Genetic determinants of virulence – Candida parapsilosis

array:23 ["pii" => "S1130140613001150" "issn" => "11301406" "doi" => "10.1016/j.riam.2013.09.018" "estado" => "S300" "fechaPublicacion" => "2014-01-01" "aid" => "285" "copyright" => "Revista Iberoamericana de Micología" "copyrightAnyo" => "2013" "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Rev Iberoam Micol. 2014;31:16-21" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2936 "formatos" => array:3 [ "EPUB" => 48 "HTML" => 2219 "PDF" => 669 ] ] "itemSiguiente" => array:18 [ "pii" => "S1130140613001113" "issn" => "11301406" "doi" => "10.1016/j.riam.2013.09.014" "estado" => "S300" "fechaPublicacion" => "2014-01-01" "aid" => "281" "copyright" => "Revista Iberoamericana de Micología" "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Rev Iberoam Micol. 2014;31:22-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3239 "formatos" => array:3 [ "EPUB" => 39 "HTML" => 2370 "PDF" => 830 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Mycologic Forum" "titulo" => "Highlights in pathogenic fungal biofilms" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "22" "paginaFinal" => "29" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Aspectos sobresalientes en la formación de biopelículas por hongos patógenos" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Janaina De Cássia Orlandi Sardi, Nayla De Souza Pitangui, Gabriela Rodríguez-Arellanes, Maria Lucia Taylor, Ana Maria Fusco-Almeida, Maria José Soares Mendes-Giannini" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Janaina De Cássia Orlandi" "apellidos" => "Sardi" ] 1 => array:2 [ "nombre" => "Nayla De Souza" "apellidos" => "Pitangui" ] 2 => array:2 [ "nombre" => "Gabriela" "apellidos" => "Rodríguez-Arellanes" ] 3 => array:2 [ "nombre" => "Maria Lucia" "apellidos" => "Taylor" ] 4 => array:2 [ "nombre" => "Ana Maria" "apellidos" => "Fusco-Almeida" ] 5 => array:2 [ "nombre" => "Maria José Soares" "apellidos" => "Mendes-Giannini" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1130140613001113?idApp=UINPBA00004N" "url" => "/11301406/0000003100000001/v1_201402070026/S1130140613001113/v1_201402070026/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S1130140613001101" "issn" => "11301406" "doi" => "10.1016/j.riam.2013.09.013" "estado" => "S300" "fechaPublicacion" => "2014-01-01" "aid" => "280" "copyright" => "Revista Iberoamericana de Micología" "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Rev Iberoam Micol. 2014;31:11-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2850 "formatos" => array:3 [ "EPUB" => 51 "HTML" => 2038 "PDF" => 761 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Mycologic Forum" "titulo" => "The importance of molecular analyses for understanding the genetic diversity of Histoplasma capsulatum: An overview" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "11" "paginaFinal" => "15" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Importancia de los análisis moleculares en la comprensión de la diversidad genética de Histoplasma capsulatum: revisión" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1428 "Ancho" => 3210 "Tamanyo" => 331269 ] ] "descripcion" => array:1 [ "en" => "Concatenated phylogenetic trees of Mexican H. capsulatum isolates using an MLS analysis. Trees were constructed with MEGA5 software considering the sequences, from 30 H. capsulatum samples, of the polymorphic loci: arf, H-anti, ole1, tub1, and the (GA)n microsatellite. Phylogenetic analyses were conducted as follows: (1) the neighbor-joining (NJ) method using the Kimura two-parameter model<a class="elsevierStyleCrossRef" href="#bib0085">17</a>; and (2) the maximum parsimony (MP) method using the close-neighbor-interchange algorithm.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> Data of parsimony were: MPT=99; LT=188; CI=0.584615; RI=0.881569. Trees were generated with 1000 replicates. Fourteen of the Mexican H. capsulatum isolates were previously classified by Kasuga et al.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> as belonging to the LAm A clade. Abbreviations: Tb (T. brasiliensis), Ah (A. hirsutus), Ln (L. nivalis), Lc (L. curasoae), Mm (M. megalophylla), Dr (Desmodus rotundus), CS (Chiapas), GR (Guerrero), HG (Hidalgo), Mn (Michoacán), MS (Morelos), NL (Nuevo León), OC (Oaxaca), PL (Puebla), and USA (United States of America)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Tania Vite-Garín, Daniel Alfonso Estrada-Bárcenas, Joaquín Cifuentes, Maria Lucia Taylor" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Tania" "apellidos" => "Vite-Garín" ] 1 => array:2 [ "nombre" => "Daniel Alfonso" "apellidos" => "Estrada-Bárcenas" ] 2 => array:2 [ "nombre" => "Joaquín" "apellidos" => "Cifuentes" ] 3 => array:2 [ "nombre" => "Maria Lucia" "apellidos" => "Taylor" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1130140613001101?idApp=UINPBA00004N" "url" => "/11301406/0000003100000001/v1_201402070026/S1130140613001101/v1_201402070026/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Mycologic Forum" "titulo" => "Genetic determinants of virulence – Candida parapsilosis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "16" "paginaFinal" => "21" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Kumara Singaravelu, Attila Gácser, Joshua D. Nosanchuk" "autores" => array:3 [ 0 => array:3 [ "nombre" => "Kumara" "apellidos" => "Singaravelu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Attila" "apellidos" => "Gácser" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:4 [ "nombre" => "Joshua D." "apellidos" => "Nosanchuk" "email" => array:1 [ 0 => "josh.nosanchuk@einstein.yu.edu" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departments of Medicine (Infectious Diseases) and Microbiology & Immunology, Albert Einstein College of Medicine, New York, NY, United States" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Microbiology, University of Szeged, Szeged, Hungary" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Determinantes genéticos de la virulencia de Candida parapsilosis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1119 "Ancho" => 1500 "Tamanyo" => 217196 ] ] "descripcion" => array:1 [ "en" => "Immunofluorescence microscopy of C. parapsilosis and human macrophages. Red yeast are dead (photo credit to C. Papp and A. Gácser)." ] ] ] "textoCompleto" => "Since the late 1970s, fungal infections have increasingly become a significant cause of morbidity and mortality especially among hospitalized and immunosuppressed patients.<a class="elsevierStyleCrossRef" href="#bib0345">69</a>Candida species are the fourth most frequent causative agent of blood-stream infections, constituting 8–15% of hospital-acquired infections.<a class="elsevierStyleCrossRef" href="#bib0435">87</a> In the United States, Candida albicans is the most common pathogen followed by Candida parapsilosis or Candida glabrata, depending on the study. However, C. parapsilosis has become the leading causative agent in some institutions located in Europe, Asia and South America, and it is the Candida species with the largest increase in incidence since 1990.<a class="elsevierStyleCrossRefs" href="#bib0005">1,6,10–12,20,36,48,52,54,70,74,81,87</a> Of all candidal isolates, C. parapsilosis accounts for 15.5% in North America, 16.3% in Europe and 23.4% in Latin America.<a class="elsevierStyleCrossRef" href="#bib0405">81</a> In the US, it has been the third most common cause of neonatal sepsis.<a class="elsevierStyleCrossRef" href="#bib0330">66</a>First isolated in 1928 from a stool specimen and thought to be non-pathogenic,<a class="elsevierStyleCrossRefs" href="#bib0010">2,86</a>C. parapsilosis is now recognized as being fairly ubiquitous as it can be isolated from humans as a normal skin commensal as well as from domestic animals, insects, soil and marine environments.<a class="elsevierStyleCrossRefs" href="#bib0095">19,81,85</a> It is now especially well documented as a pathogen that arises from exogenous sources of infection in intravenous drug users and via medical instrumentation (e.g. catheters and hyperalimentation solutions).<a class="elsevierStyleCrossRefs" href="#bib0170">34,81</a> In particular, C. parapsilosis is recognized for its ability to cause invasive disease in patients without prior evidence of colonization via horizontal transmission through medical devices including catheters, parenteral nutrition solutions, and the hands of healthcare workers.<a class="elsevierStyleCrossRef" href="#bib0405">81</a> Invasive disease occurs more often in immunocompromised patients, such as individuals with AIDS, cancer and in patients undergoing gastrointestinal surgical procedures.<a class="elsevierStyleCrossRef" href="#bib0405">81</a> Other risk factors reported in studies include transplant receipt, antibiotic exposure, ophthalmic irrigating solutions and, especially, low birth weight in premature neonates.<a class="elsevierStyleCrossRefs" href="#bib0005">1,44,78,85,86</a> Clinical manifestations of C. parapsilosis include endocarditis, meningitis, peritonitis, arthritis, endophthalmitis, keratitis, otomycosis, onychomycosis, vulvovaginitis and urinary tract infections.<a class="elsevierStyleCrossRef" href="#bib0405">81</a> Mortality rates attributed to C. parapsilosis range from 4% to 45%, with an average mortality rate of 28.5%.<a class="elsevierStyleCrossRefs" href="#bib0030">6,11,28,81</a> Biofilm producing isolates are associated with outbreaks<a class="elsevierStyleCrossRef" href="#bib0190">38</a> and significantly higher mortality rates.<a class="elsevierStyleCrossRef" href="#bib0410">82</a>Determinants of virulence for candidal disease include adhesion capability to host surface, ability to switch morphology between yeast and filamentous growth, biofilm formation and secretion of extracellular hydrolytic enzymes such as lipases, phospholipases or secreted aspartyl proteinases.<a class="elsevierStyleCrossRefs" href="#bib0255">51,83</a> Conflicting data exist regarding phospholipase activity, with some studies demonstrating their presence in clinical isolates and others their absence.<a class="elsevierStyleCrossRefs" href="#bib0070">14,16,26,47</a> Nevertheless, its role in virulence bears consideration. The development of gene disruption methods to produce mutants has been a pivotal achievement in our capacity to gain insights into the interactions of C. parapsilosis with hosts and host effector cells (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>). This review will focus on the observations made on specific genes that have so far been characterized and shown to significantly influence these virulence traits.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>Gene disruptionC. parapsilosis has a diploid genome and does not have a described sexual cycle. Genetic analysis was initially limited by the availability of appropriate study tools. The first targeted gene disruption method was developed in 2007<a class="elsevierStyleCrossRef" href="#bib0115">23</a> based on previously established gene disruption protocols in C. albicans. The first targeted deletion in C. parapsilosis was the disruption of secreted lipases. This efficient gene deletion system was developed utilizing the repeated use of the dominant nourseoethricin marker (caSAT1) and subsequent deletion by FLP-mediated, site-specific recombination.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> Applying this technique, the lipase locus in C. parapsilosis containing the adjacent lipase genes CpLIP1, CpLIP2 were deleted and CPLIP2 reconstructed providing an understanding of the role of lipase activity in virulence.<a class="elsevierStyleCrossRef" href="#bib0115">23</a>LipasesMicrobial extracellular lipases are virulence factors in a broad range of bacteria and fungi, including Candida species.<a class="elsevierStyleCrossRef" href="#bib0405">81</a> So far, 10 lipase genes have been identified in C. albicans,<a class="elsevierStyleCrossRef" href="#bib0160">32</a> and disruption, such as the deletion of LIP8, can significantly affect virulence.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> Only two lipase genes have been elucidated in C. parapsilosis – CpLIP1 and CpLIP2, of which only the latter has been demonstrated to code for an active protein.<a class="elsevierStyleCrossRefs" href="#bib0035">7,53</a> Utilizing the described targeted gene deletion method, disruption of these lipase genes provides evidence that they play a role in pathogenesis (i) by the decreased tissue damage seen in the presence of lipase inhibitors, (ii) the decreased ability of CpLIP1-CpLIP2 homozygous mutants to form complex biofilms, (iii) requirement for lipid-rich media, (iv) increased susceptibility to phagocytosis by macrophage-like cells, and (v) decreased virulence in comparison to wild-type C. parapsilosis yeast in infections of human oral epithelium or during murine intraperitoneal challenges.<a class="elsevierStyleCrossRefs" href="#bib0105">21,23</a> These observations hold significant clinical relevance since C. parapsilosis infections are particularly more commonly seen in patients receiving lipid-rich total parenteral nutrition and thus lipases may be a potential target for future antifungal agent development.<a class="elsevierStyleCrossRef" href="#bib0405">81</a>Secreted aspartyl proteinase (Sap)Secreted aspartyl proteinase (Sap) genes have been demonstrated in most pathogenic Candida including C. albicans, Candida dubliniensis, Candida tropicalis and C. parapsilosis.<a class="elsevierStyleCrossRefs" href="#bib0125">25,45,49,89</a> However, they are notably absent in many non-pathogenic yeasts (e.g. Saccharomyces cerevisiae) suggesting their possible role in virulence.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> Sap isoenzymes have several functions such as (i) digestion of host proteins for provision of nitrogen sources, (ii) degradation of host cell surface structure and intracellular substances promoting tissue adhesion and invasion, and (iii) destruction of cells and molecules of the host immune system such as immunoglobulin G heavy chains, 2-macroglobulin, C3 protein, lactoglobulin, lactoperoxidase, collagen, and fibronectin<a class="elsevierStyleCrossRefs" href="#bib0355">71,77</a> thereby enabling evasion of antimicrobial activity.<a class="elsevierStyleCrossRef" href="#bib0155">31</a> For example, vulvovaginal and skin C. albicans isolates exhibit higher in vitro Sap activity compared to blood isolates, which possibly explains the earlier clearance of fungemia in comparison to sustained skin infection in infection models.<a class="elsevierStyleCrossRefs" href="#bib0040">8,14,15,88</a> To date, ten SAP genes (Sap1p-Sap10p) have been identified in C. albicans.<a class="elsevierStyleCrossRef" href="#bib0255">51</a> Their role in C. parapsilosis was unclear until the recent identification of 2 SAPP1 genes: SAPP1a and SAPP1b.<a class="elsevierStyleCrossRef" href="#bib0150">30</a>The C. parapsilosis genome database (<a id="intr0005" class="elsevierStyleInterRef" href="http://www.sanger.ac.uk/sequencing/candida/parapsilosis">www.sanger.ac.uk/sequencing/candida/parapsilosis</a>) was used to perform in silico analysis of the SAPP1 genes. A 2871 base pair-duplicated upstream (SAPP1a) and downstream (SAPP1b) regions were defined in the genome.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> All 4 alleles of the SAPP1 gene were deleted from wild-type (WT) C. parapsilosis.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> Separate homozygous ΔΔsapp1a, ΔΔsapp1b and a double-homozygous mutant ΔΔsapp1a-ΔΔsapp1b were generated.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> Subsequent experiments revealed that in an inducer medium, Sapp1p production was reduced by about 50% in the ΔΔsapp1a and ΔΔsapp1b mutants, but a similar effect was not observed for the SAPP2 gene. On the other hand, Sapp2p production was greater in the ΔΔsapp1a-ΔΔsapp1b mutant compared to wild-type yeast. This mutant was also hyper-susceptible to human serum, had decreased proteolytic activity, and decreased capacity to damage host-effector cells. Additionally, there was also greater phagocytosis and killing of the ΔΔsapp1a-ΔΔsapp1b yeasts by both human peripheral blood mononuclear cells (PBMCs) and PBMC-derived macrophages (PBMC-DM). After phagocytosis, the ΔΔsapp1a-ΔΔsapp1b yeasts induced more frequent phagolysosomal fusion, suggesting a role for Sapp1p in promoting intracellular survival.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> Both the lipase and proteinase genes play a major role in biofilm formation which is the hallmark of both bacterial and fungal organisms involved in device related infection. While the basic characteristics for biofilm formation may be similar among biofilm producing organisms, unique differences exist as well.Biofilm formationColonization and infection due to C. parapsilosis are initiated by the organism's ability to adhere to host cells and tissues followed by the formation of biofilm on medical devices,<a class="elsevierStyleCrossRef" href="#bib0405">81</a> which is accomplished in part by cell surface hydrophobicity<a class="elsevierStyleCrossRef" href="#bib0335">67</a> and slime production.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Compared to C. albicans, C. parapsilosis has a 20.6% greater avidity to buccal epithelial cells and 143.7% increased adhesiveness to acrylic material,<a class="elsevierStyleCrossRef" href="#bib0335">67</a> although smaller studies have shown less significant differences.<a class="elsevierStyleCrossRef" href="#bib0405">81</a> After adherence, biofilm formation is initiated by the establishment of cellular layers via cell-to-cell contact.<a class="elsevierStyleCrossRef" href="#bib0375">75</a> In C. albicans, after adherence to tissues, the cells transform from yeast to hyphal forms, which appear to be a requirement for a structured biofilm.<a class="elsevierStyleCrossRefs" href="#bib0015">3,73</a> Once the mature biofilm is formed it is covered by an extracellular matrix that renders it less susceptible to antifungal medications. The transcriptional changes that occur during this process have been well studied in C. albicans, which reveal significant increases in the expression of genes that participate in glycolysis, amino acid and lipid metabolism.<a class="elsevierStyleCrossRefs" href="#bib0120">24,50</a>C. parapsilosis and C. albicans differ in the nature of the biofilm formed. C. parapsilosis forms smaller and less complex structures,<a class="elsevierStyleCrossRefs" href="#bib0145">29,37</a> possibly because they do not produce hyphae. C. parapsilosis biofilms consist of yeast and pseudohyphal cells.<a class="elsevierStyleCrossRefs" href="#bib0085">17,23,37</a> Of note, pseudohyphal phenotypes can generate more biofilm and exhibit greater invasiveness into agar than strains in yeast forms.<a class="elsevierStyleCrossRef" href="#bib0210">42</a> Similarities exist as well between the two species: biofilms of both are inhibited by exogenous farnesol<a class="elsevierStyleCrossRefs" href="#bib0210">42,76</a> and Bcr1 (Biofilm and Cell wall Regulator 1) is a major regulator for both species.<a class="elsevierStyleCrossRefs" href="#bib0085">17,60,61</a>BCR1In vivo rat catheter models have been utilized to describe the role of BCR1 in the development of biofilms.<a class="elsevierStyleCrossRef" href="#bib0090">18</a>BCR1 has been demonstrated to be a required fungal transcription factor for the formation of biofilms in both C. albicans and C. parapsilosis.<a class="elsevierStyleCrossRefs" href="#bib0085">17,60,61</a> Deletion of BCR1 in either species impairs the ability for biofilm formation.<a class="elsevierStyleCrossRefs" href="#bib0085">17,61</a> In C. albicans, BCR1 encodes genes targeting adhesins and cell-wall proteins (ALS1, ALS3, HWP1 and RBT5) indicating its role in the early adhesive stages of biofilm formation.<a class="elsevierStyleCrossRefs" href="#bib0300">60–63</a> The effect of Bcr1 on biofilm formation is also thought to be in part secondary to its influence on the expression of CFEM (Common in Fungal Extracellular Membranes) family of proteins. CFEMs were initially identified in Magnaportha grisea. They are similar to epidermal growth factor (EGF) domains that are found in extracellular membrane regions and contain an eight-cysteine domain.<a class="elsevierStyleCrossRefs" href="#bib0195">39,40</a> The role of CFEM is likely to act as cell surface receptors (adhesins).<a class="elsevierStyleCrossRef" href="#bib0195">39</a> At least 5 CFEM members have been identified in C. albicans: PGA7, PGA10, RBT5, CSA1 and CSA2. Three of them, PGA10, RBT5 and CSA1, have been identified as vital for biofilm development.<a class="elsevierStyleCrossRef" href="#bib0340">68</a>C. parapsilosis has seven CFEM members (CFEM1-CFEM7) including tandem duplicates of orthologs of C. albicans RBT5, PGA10 and CSA1.<a class="elsevierStyleCrossRef" href="#bib0090">18</a>CFEM1-CFEM4 are in tandem and syntenic with RBT5 and PGA-7, which in C. parapsilosis is postulated to have single gene duplications thereby forming CFEM1/CFEM2 and CFEM3/CFEM4. CFEM5-6 are orthologous with CSA1. An ortholog of CFEM7 has not been identified in the Candida clade and may possibly be specific to C. parapsilosis.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> Bcr1 exerts a different influence on the CFEM family in C. parapsilosis. In Bcr1d mutants, one member of each orthologous pair of CFEM2, CFEM3 and CFEM6 are down regulated, whereas expression of CFEM1, CFEM4, CFEM5 and CFEM7 is not affected.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> Interestingly, CFEM 2, CFEM3 or CFEM6 do not appear to be a requirement for the formation of biofilms in C. parapsilosis. CFEM2 and CFEM3 are necessary and CFEM6 is partially required for the heme utilization. Global transcriptional profiling of cells in an iron-depleted environment has shown the increased expression of 59 genes and decrease in 89 genes. Increased expression occurred in genes linked with cellular iron ion hemostasis and iron ion transport (FTH1, FRE9 and FRE10). Decreased expression was seen in heme containing and iron sulfur proteins (YHB1, SDH2 and ISA1) and all mitochondrial genes.<a class="elsevierStyleCrossRef" href="#bib0090">18</a>RBT1When C. parapsilosis produces biofilms there is an upregulation of the genes involved in the glycolysis, fatty acid metabolism and ergosterol synthesis.<a class="elsevierStyleCrossRef" href="#bib0375">75</a> These changes are similar to the ones observed when C. albicans cells are grown under hypoxic conditions.<a class="elsevierStyleCrossRef" href="#bib0395">79</a> Although C. parapsilosis does not produce true hyphae, the genome includes a member of the hyphae producing gene family, Hwp1.<a class="elsevierStyleCrossRef" href="#bib0380">76</a> One of the members in this family, the gene RBT1 is induced during the production of biofilms and under hypoxia.<a class="elsevierStyleCrossRef" href="#bib0380">76</a> In C. albicans, RBT1 is induced during filamentation and mutants have been demonstrated to have decreased virulence in rabbit and mouse cornea models.<a class="elsevierStyleCrossRefs" href="#bib0025">5,33</a> In C. parapsilosis, RBT1 knockout isolates produce structurally much thinner biofilms than wild type while the heterozygous strains produce an intermediate thickness biofilm. This suggests that for full and appropriate biofilm development both of the RBT1 alleles are required.<a class="elsevierStyleCrossRef" href="#bib0375">75</a>Lipid metabolismFatty acid formation is vital for the functioning of organisms in all kingdoms. They are building blocks of cell membranes that are products of cellular biosynthesis and require a complex enzyme system.<a class="elsevierStyleCrossRef" href="#bib0290">58</a> So far, three major fatty acid synthesis systems have been identified. Eukaryotes and advanced prokaryotes (Mycobacterium, Nocardia and Corynebacterium) utilize Type I Fatty Acid synthesis system (FAS1), most bacteria utilize Type II, and parasites such as Trypanosma and Leishmania use FAS3.<a class="elsevierStyleCrossRef" href="#bib0215">43</a> While similar enzymes are found in the three FAS systems, the organization of the encoding genes may significantly vary.<a class="elsevierStyleCrossRef" href="#bib0290">58</a> In fungal organisms, production of essential fatty acids such as saturated and unsaturated fatty acids is critical for the generation and maintenance of cell membranes. Fatty acid synthase (FAS) and fatty acid desaturase (OLE) are important enzymes in this pathway.<a class="elsevierStyleCrossRef" href="#bib0275">55</a>Fatty acid synthaseFungal FAS enzymes initiate the formation of a 2,6-MD heterodacemeric complex including subunits that are encoded by FAS1 and FAS2.<a class="elsevierStyleCrossRef" href="#bib0290">58</a> These enzymes are therefore critical for normal yeast growth, and disruption of even a single gene can significantly alter the organisms’ physiological phenotype and virulence. Fas2 inhibition has been demonstrated to attenuate pathogenicity of Cryptococcus neoformans, C. parapsilosis and C. albicans.<a class="elsevierStyleCrossRefs" href="#bib0045">9,90,91</a>C. parapsilosis Fas2 (encoded by CpFAS2) heterozygous, homozygous and reconstituted Fas2 mutants have been generated.<a class="elsevierStyleCrossRef" href="#bib0290">58</a>CpFAS2 is required for growth in standard medium and gene expression was repressed in the presence of fatty acids.<a class="elsevierStyleCrossRef" href="#bib0290">58</a> Further, up-regulation of CpFAS2 occurred when only glucose was made available as the carbon source. In comparison to a wild type yeast, CpFAS2 disruptants had a significant decrease in the concentration of unsaturated fatty acids.<a class="elsevierStyleCrossRef" href="#bib0290">58</a>CpFAS2 genes are also necessary for normal biofilm formation. Microarray studies demonstrate that CpFAS2 is upregulated during in vitro biofilm formation under hypoxic stress. Δfas2 strains were shown to have decreased capability for biofilm formation on polystyrene and silicone surfaces.<a class="elsevierStyleCrossRef" href="#bib0290">58</a>CpFAS2 also appears to play a vital role in helping the organism survive the fungicidal activity of monocytes such as neutrophils and macrophages. Intracellular survival of CpFAS2 disruptants was reduced by 40% when compared with wild type and heterozygous strains with a single FAS2 gene.<a class="elsevierStyleCrossRef" href="#bib0290">58</a> This decrease in survival could likely be due to diminished membrane stability, thereby enhancing susceptibility to reactive oxygen species secreted by the macrophages. The Δfas2 strains demonstrate a leaky phenotype when grown under stress conditions. This action, in combination with defective fatty acid production, alters intracellular viability and proliferation of strains with CpFAS2 deletion.<a class="elsevierStyleCrossRef" href="#bib0290">58</a>The Fas2 enzyme also appears to be critical for survival of C. parapsilosis in serum.<a class="elsevierStyleCrossRef" href="#bib0275">55</a> This is a vital process in fungal pathogenesis as exposure to serum influences virulence traits such as filamentation and biofilm formation.<a class="elsevierStyleCrossRef" href="#bib0295">59</a> Efficacy of antifungal drugs is decreased in serum, making the eradication of systemic infections difficult.<a class="elsevierStyleCrossRef" href="#bib0325">65</a>CpFAS2 disruptants are hypersensitive to serum and induce cell death.<a class="elsevierStyleCrossRef" href="#bib0275">55</a> Cell survival also appears to be influenced by the presence of glucose, which causes mitochondria-dependent cell death. Mechanisms of glucose toxicity in Δfas2 strains are yet unclear, as glucose is usually a preferred carbon source for normal yeast growth. Toxicity may potentially be secondary to uncontrolled metabolism of glucose by the mutant cells, thereby creating an imbalance of cellular contents and subsequent triggering of a cell death response,<a class="elsevierStyleCrossRef" href="#bib0275">55</a> especially via energy-requiring apoptosis pathways, overproduction of ROS, nuclear fragmentation and cell shrinkage.<a class="elsevierStyleCrossRefs" href="#bib0135">27,84</a>Fatty acid desaturase (OLE1)In addition to glucotoxicity, elevated lipid content is thought to be detrimental to normal yeast growth.<a class="elsevierStyleCrossRef" href="#bib0285">57</a> In C. parapsilosis, exposure to high glucose induces formation of lipid droplets (LD); it is considered a possible mechanism through which yeast cells survive gluco- and lipo-toxicity.<a class="elsevierStyleCrossRef" href="#bib0285">57</a> Both the CpFAS2 and fatty acid desaturase genes (OLE1) appear to play a role. Disruption of either of these genes inhibits LD formation from glucose.<a class="elsevierStyleCrossRef" href="#bib0285">57</a> Moreover, OLE1 inhibition resulted in gluco/lipotoxicity of log phage yeast cells. While survival of wild type yeasts was decreased after 2 days of incubation, Δole1 mutants died within a few hours of incubation, indicating its role in glucose detoxification.<a class="elsevierStyleCrossRef" href="#bib0285">57</a> In addition to glucose, OLE1 deletion strains are also hypersusceptible to fructose, galactose, and mannose.FIT2Lipid droplets (LDs) are cytoplasmic compartments that contain triacylglycerides (TAGs) that serve as fatty acid reservoirs<a class="elsevierStyleCrossRef" href="#bib0230">46</a> and lipid precursors of fatty acids (FA) and diacyl glycerol (DAG) for membrane lipids such as glycerophospholipids and sphingolipids.<a class="elsevierStyleCrossRefs" href="#bib0065">13,41</a> TAGs and steryl esters are major components of LDs and utilize fatty acyl CoA as a common substrate.<a class="elsevierStyleCrossRef" href="#bib0360">72</a> Akin to mammalian cells, LDs may significantly influence the functioning of pathogenic fungi. In C. parapsilosis, formation of LDs is necessary for normal cell growth and virulence.<a class="elsevierStyleCrossRef" href="#bib0280">56</a> A family of proteins involved in LD formation – fat storage-inducing transmembrane proteins 1 and 2 (FIT1 and FIT2) – has recently been demonstrated in both humans and mice.<a class="elsevierStyleCrossRefs" href="#bib0175">35,56</a> In mammalian cells, FIT2 orthologs enable compartmentalization of TAG in LDs and depleting FIT2 transcripts in adipocytes decreased LD formation.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> The FIT2 proteins are primarily localized to the endoplasmic reticulum and are responsible for lipid partitioning rather than lipid synthesis.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> Effects of FIT2 on LD accumulation are therefore likely downstream in comparison to the DGA1 pathway.<a class="elsevierStyleCrossRefs" href="#bib0320">64,80</a>In C. parapsilosis, disruption of FIT2 impairs LD formation, alters the lipidome and attenuates virulence.<a class="elsevierStyleCrossRef" href="#bib0280">56</a> Both in vitro and in vivo studies demonstrated that heterozygous strains with deletion of one FIT2 allele did not decrease TAG formation or LD size. However, deletion of both FIT2 alleles significantly decreased TAG content (39%) and LD accumulation.<a class="elsevierStyleCrossRef" href="#bib0280">56</a> Alterations were also noted in other lipid species with FIT2 deletion. While a 25% reduction was observed in fatty acids (FFA), unsaturated fatty oleic (4.63%) and linoleic acids (12.31%), elevations were noted in steryl esters (135%), diacylglycerols/sterols (96%) and phospholipids (112%), palmitic (1.5%) and stearic acids (15%).<a class="elsevierStyleCrossRef" href="#bib0280">56</a> However, FIT2 deletion did not alter susceptibility to standard antifungal drugs.ConclusionsThe epidemiology of microorganisms that impact human morbidity and mortality is constantly evolving. Globally, there is increased life expectancy, improved and more frequent access to the healthcare system, rising use of immunosuppressants, immunomodulators and biologics, and increased utilization of indwelling devices such as catheters and cardiovascular devices. Microbes that have the ability to evade the host immune system, produce biofilms and develop resistance to available treatment options have and will significantly impact morbidity and mortality. This is well exemplified by the globally increasing prevalence of C. parapsilosis infections. A significant work has been accomplished in identifying the genetic factors that determine the organism's virulence, and increased efforts are urgently needed to counter this global threat.Conflict of interestsThe authors have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:2 [ "identificador" => "xres311208" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec294362" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres311209" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec294361" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Gene disruption" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Lipases" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Secreted aspartyl proteinase (Sap)" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Biofilm formation" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "BCR1" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "RBT1" ] ] ] 8 => array:3 [ "identificador" => "sec0035" "titulo" => "Lipid metabolism" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Fatty acid synthase" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Fatty acid desaturase (OLE1)" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "FIT2" ] ] ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Conclusions" ] 10 => array:2 [ "identificador" => "sec0060" "titulo" => "Conflict of interests" ] 11 => array:2 [ "identificador" => "xack73815" "titulo" => "Acknowledgements" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-08-15" "fechaAceptado" => "2013-09-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec294362" "palabras" => array:8 [ 0 => "Candida parapsilosis" 1 => "Gene disruption" 2 => "Lipase" 3 => "Secreted aspartyl proteinases" 4 => "Phospholipase" 5 => "Fatty acid biosynthesis" 6 => "Biofilm" 7 => "Virulence" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec294361" "palabras" => array:8 [ 0 => "Candida parapsilosis" 1 => "Alteración génica" 2 => "Lipasa" 3 => "Secreción de aspartilproteinasas" 4 => "Fosfolipasa" 5 => "Biosíntesis de ácidos grasos" 6 => "Biopelícula" 7 => "Virulencia" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "The global epidemiology of fungal infections is changing. While overall, Candida albicans remains the most common pathogen; several institutions in Europe, Asia and South America have reported the rapid emergence to predominance of Candida parapsilosis. This mini-review examines the impact of gene deletions achieved in C. parapsilosis that have been published to date. The molecular approaches to gene disruption in C. parapsilosis and the molecularly characterized genes to date are reviewed. Similar to C. albicans, factors influencing virulence in C. parapsilosis include adherence, biofilm formation, lipid metabolism, and secretion of hydrolytic enzymes such as lipases, phospholipases and secreted aspartyl proteinases. Development of a targeted gene deletion method has enabled the identification of several unique aspects of C. parapsilosis genes that play a role in host–pathogen interactions – CpLIP1, CpLIP2, SAPP1a, SAPP1b, BCR1, RBT1, CpFAS2, OLE1, FIT-2.This manuscript is part of the series of works presented at the “V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi” (Oaxaca, Mexico, 2012)." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La epidemiología mundial de las infecciones fúngicas está cambiando. Aunque Candida albicans sigue siendo el patógeno más común, varios centros en Europa, Asia y Sudamérica han descrito la rápida emergencia de Candida parapsilosis, que ha terminado por predominar. La presente revisión examina la influencia de las deleciones genéticas producidas en C. parapsilosis que se han publicado hasta la fecha. Se revisan las estrategias moleculares de la alteración de genes de C. parapsilosis y los genes caracterizados molecularmente hasta la fecha. Al igual que en C. albicans, los factores que influyen en la virulencia de C. parapsilosis incluyen la adherencia, formación de biopelículas, el metabolismo de lípidos y la secreción de enzimas hidrolíticas, como lipasas, fosfolipasas y aspartilproteinasas. El desarrollo de un método de deleción génica dirigido ha permitido la identificación de varios aspectos exclusivos de los genes de C. parapsilosis que participan en las interacciones huésped-patógeno-CpLIP1, CpLIP2, SAPP1a, SAPP1b, BCR1, RBT1, CpFAS2, OLE1, FIT-2.Este artículo forma parte de una serie de estudios presentados en el «V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi» (Oaxaca, México, 2012)." ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1126 "Ancho" => 1500 "Tamanyo" => 200449 ] ] "descripcion" => array:1 [ "en" => "Scanning electron microscopy of C. parapsilosis interacting with murine macrophages (photo credit to T. Németh, T. Petkovits, and A. Gácser)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1119 "Ancho" => 1500 "Tamanyo" => 217196 ] ] "descripcion" => array:1 [ "en" => "Immunofluorescence microscopy of C. parapsilosis and human macrophages. Red yeast are dead (photo credit to C. Papp and A. Gácser)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:91 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology, risk factors, and prognosis of Candida parapsilosis bloodstream infections: case-control population-based surveillance study of patients in Barcelona, Spain, from 2002 to 2003" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Almirante" 1 => "D. Rodriguez" 2 => "M. Cuenca-Estrella" 3 => "M. Almela" 4 => "F. Sanchez" 5 => "J. Ayats" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/JCM.44.5.1681-1685.2006" "Revista" => array:6 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "2006" "volumen" => "44" "paginaInicial" => "1681" "paginaFinal" => "1685" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16672393" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Certain conditions of the gastrointestinal tract in Puerto Rico and their relation to tropical sprue" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "B. Ashford" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Am J Trop Med Hyg" "fecha" => "1928" "volumen" => "8" "paginaInicial" => "507" "paginaFinal" => "538" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of dimorphism in the development of Candida albicans biofilms" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "G.S. Baillie" 1 => "L.J. Douglas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1099/00222615-48-7-671" "Revista" => array:6 [ "tituloSerie" => "J Med Microbiol" "fecha" => "1999" "volumen" => "48" "paginaInicial" => "671" "paginaFinal" => "679" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10403418" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genotypic variation and slime production among blood and catheter isolates of Candida parapsilosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.L. Branchini" 1 => "M.A. Pfaller" 2 => "J. Rhine-Chalberg" 3 => "T. Frempong" 4 => "H.D. Isenberg" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "1994" "volumen" => "32" "paginaInicial" => "452" "paginaFinal" => "456" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification and characterization of TUP1-regulated genes in Candida albicans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "B.R. Braun" 1 => "W.S. Head" 2 => "M.X. Wang" 3 => "A.D. Johnson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Genetics" "fecha" => "2000" "volumen" => "156" "paginaInicial" => "31" "paginaFinal" => "44" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical and microbiological aspects of candidemia due to Candida parapsilosis in Brazilian tertiary care hospitals" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.R. Brito" 1 => "T. Guimaraes" 2 => "M. Nucci" 3 => "R.C. Rosas" 4 => "L. Paula Almeida" 5 => "D.A. Da Matta" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/13693780500421476" "Revista" => array:6 [ "tituloSerie" => "Med Mycol" "fecha" => "2006" "volumen" => "44" "paginaInicial" => "261" "paginaFinal" => "266" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16702106" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High-level expression of Candida parapsilosis lipase/acyltransferase in Pichia pastoris" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Brunel" 1 => "V. Neugnot" 2 => "L. Landucci" 3 => "H. Boze" 4 => "G. Moulin" 5 => "F. Bigey" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jbiotec.2004.03.007" "Revista" => array:6 [ "tituloSerie" => "J Biotechnol" "fecha" => "2004" "volumen" => "111" "paginaInicial" => "41" "paginaFinal" => "50" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15196768" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biotype diversity of Candida parapsilosis and its relationship to the clinical source and experimental pathogenicity" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Cassone" 1 => "F. De Bernardis" 2 => "E. Pontieri" 3 => "G. Carruba" 4 => "C. Girmenia" 5 => "P. Martino" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Infect Dis" "fecha" => "1995" "volumen" => "171" "paginaInicial" => "967" "paginaFinal" => "975" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7706826" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fatty acid synthesis is essential for survival of Cryptococcus neoformans and a potential fungicidal target" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Chayakulkeeree" 1 => "T.H. Rude" 2 => "D.L. Toffaletti" 3 => "J.R. Perfect" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/AAC.00442-07" "Revista" => array:6 [ "tituloSerie" => "Antimicrob Agents Chemother" "fecha" => "2007" "volumen" => "51" "paginaInicial" => "3537" "paginaFinal" => "3545" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17698629" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prospective observational study of candidemia in Sao Paulo, Brazil: incidence rate, epidemiology, and predictors of mortality" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.L. Colombo" 1 => "T. Guimaraes" 2 => "L.R. Silva" 3 => "L.P. de Almeida Monfardini" 4 => "A.K. Cunha" 5 => "P. Rady" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/513615" "Revista" => array:6 [ "tituloSerie" => "Infect Control Hosp Epidemiol" "fecha" => "2007" "volumen" => "28" "paginaInicial" => "570" "paginaFinal" => "576" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17464917" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of candidemia in Brazil: a nationwide sentinel surveillance of candidemia in eleven medical centers" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.L. Colombo" 1 => "M. Nucci" 2 => "B.J. Park" 3 => "S.A. Nouer" 4 => "B. Arthington-Skaggs" 5 => "D.A. da Matta" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/JCM.00773-06" "Revista" => array:6 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "2006" "volumen" => "44" "paginaInicial" => "2816" "paginaFinal" => "2823" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16891497" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A first Portuguese epidemiological survey of fungaemia in a university hospital" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Costa-de-Oliveira" 1 => "C. Pina-Vaz" 2 => "D. Mendonca" 3 => "A. Goncalves Rodrigues" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10096-007-0448-4" "Revista" => array:6 [ "tituloSerie" => "Eur J Clin Microbiol Infect Dis" "fecha" => "2008" "volumen" => "27" "paginaInicial" => "365" "paginaFinal" => "374" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18204871" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Synthesis, storage and degradation of neutral lipids in yeast" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "T. Czabany" 1 => "K. Athenstaedt" 2 => "G. Daum" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbalip.2006.07.001" "Revista" => array:6 [ "tituloSerie" => "Biochim Biophys Acta" "fecha" => "2007" "volumen" => "1771" "paginaInicial" => "299" "paginaFinal" => "309" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16916618" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acid proteinase, phospholipase and adherence properties of Candida parapsilosis strains isolated from clinical specimens of hospitalised patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Dagdeviren" 1 => "N. Cerikcioglu" 2 => "M. Karavus" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1439-0507.2005.01145.x" "Revista" => array:6 [ "tituloSerie" => "Mycoses" "fecha" => "2005" "volumen" => "48" "paginaInicial" => "321" "paginaFinal" => "326" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16115102" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biotyping and virulence properties of skin isolates of Candida parapsilosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "F. De Bernardis" 1 => "F. Mondello" 2 => "R. San Millan" 3 => "J. Ponton" 4 => "A. Cassone" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "1999" "volumen" => "37" "paginaInicial" => "3481" "paginaFinal" => "3486" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10523538" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "In vitro differential activity of phospholipases and acid proteinases of clinical isolates of Candida" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. D’Eca Junior" 1 => "A.F. Silva" 2 => "F.C. Rosa" 3 => "S.G. Monteiro" 4 => "P. de Maria Silva Figueiredo" 5 => "C. de Andrade Monteiro" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Soc Bras Med Trop" "fecha" => "2011" "volumen" => "44" "paginaInicial" => "334" "paginaFinal" => "338" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21901875" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Development of a gene knockout system in Candida parapsilosis reveals a conserved role for BCR1 in biofilm formation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/EC.00136-07" "Revista" => array:6 [ "tituloSerie" => "Eukaryot Cell" "fecha" => "2007" "volumen" => "6" "paginaInicial" => "1310" "paginaFinal" => "1319" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Conserved and divergent roles of Bcr1 and CFEM proteins in Candida parapsilosis and Candida albicans" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0028151" "Revista" => array:5 [ "tituloSerie" => "PLoS One" "fecha" => "2011" "volumen" => "6" "paginaInicial" => "e28151" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systematics of yeast species in the Candida parapsilosis group" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Mycopathol Mycol Appl" "fecha" => "1967" "volumen" => "32" "paginaInicial" => "177" "paginaFinal" => "193" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Changing incidence of Candida bloodstream infections among NICU patients in the United States: 1995–2004" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1542/peds.2005-1996" "Revista" => array:6 [ "tituloSerie" => "Pediatrics" "fecha" => "2006" "volumen" => "117" "paginaInicial" => "1680" "paginaFinal" => "1687" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Virulence of Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis in reconstituted human tissue models" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.fgb.2007.02.002" "Revista" => array:6 [ "tituloSerie" => "Fungal Genet Biol" "fecha" => "2007" "volumen" => "44" "paginaInicial" => "1336" "paginaFinal" => "1341" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lipase 8 affects the pathogenesis of Candida albicans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Infect Immun" "fecha" => "2007" "volumen" => "75" "paginaInicial" => "4710" "paginaFinal" => "4718" ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Targeted gene deletion in Candida parapsilosis demonstrates the role of secreted lipase in virulence" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Clin Invest" "fecha" => "2007" "volumen" => "117" "paginaInicial" => "3049" "paginaFinal" => "3058" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Candida albicans biofilms: a developmental state associated with specific and stable gene expression patterns" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Eukaryot Cell" "fecha" => "2004" "volumen" => "3" "paginaInicial" => "536" "paginaFinal" => "545" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Candida dubliniensis: phylogeny and putative virulence factors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1099/00221287-144-4-829" "Revista" => array:6 [ "tituloSerie" => "Microbiology" "fecha" => "1998" "volumen" => "144" "paginaInicial" => "829" "paginaFinal" => "838" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acid proteinase, phospholipase, and biofilm production of Candida species isolated from blood cultures" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11046-007-9053-4" "Revista" => array:6 [ "tituloSerie" => "Mycopathologia" "fecha" => "2007" "volumen" => "164" "paginaInicial" => "265" "paginaFinal" => "269" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sugar-induced apoptosis in yeast cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "FEMS Yeast Res" "fecha" => "2003" "volumen" => "4" "paginaInicial" => "7" "paginaFinal" => "13" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Attributable mortality of nosocomial candidemia, revisited" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/378745" "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2003" "volumen" => "37" "paginaInicial" => "1172" "paginaFinal" => "1177" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biofilm formation by Candida species on the surface of catheter materials in vitro" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Infect Immun" "fecha" => "1994" "volumen" => "62" "paginaInicial" => "915" "paginaFinal" => "921" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The identification of gene duplication and the role of secreted aspartyl proteinase 1 in Candida parapsilosis virulence" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/infdis/jir873" "Revista" => array:6 [ "tituloSerie" => "J Infect Dis" "fecha" => "2012" "volumen" => "205" "paginaInicial" => "923" "paginaFinal" => "933" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Candida albicans proteinases: resolving the mystery of a gene family" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1099/00221287-147-8-1997" "Revista" => array:6 [ "tituloSerie" => "Microbiology" "fecha" => "2001" "volumen" => "147" "paginaInicial" => "1997" "paginaFinal" => "2005" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Secreted lipases of Candida albicans: cloning, characterisation and expression analysis of a new gene family with at least ten members" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Microbiol" "fecha" => "2000" "volumen" => "174" "paginaInicial" => "362" "paginaFinal" => "374" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Corneal virulence of Candida albicans strains deficient in Tup1-regulated genes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Invest Ophthalmol Vis Sci" "fecha" => "2007" "volumen" => "48" "paginaInicial" => "2535" "paginaFinal" => "2539" ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Subacute endocarditis and systemic mycosis (monilia)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "JAMA" "fecha" => "1940" "volumen" => "115" "paginaInicial" => "205" "paginaFinal" => "208" ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evolutionarily conserved gene family important for fat storage" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.0708579105" "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci USA" "fecha" => "2008" "volumen" => "105" "paginaInicial" => "94" "paginaFinal" => "99" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fungemia in neonates: report of 80 cases from seven University hospitals" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Pediatrics" "fecha" => "2000" "volumen" => "105" "paginaInicial" => "913" "paginaFinal" => "914" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of biofilms formed by Candida albicans and Candida parapsilosis on bioprosthetic surfaces" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Infect Immun" "fecha" => "2002" "volumen" => "70" "paginaInicial" => "878" "paginaFinal" => "888" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Candida parapsilosis characterization in an outbreak setting" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3201/eid1006.030873" "Revista" => array:6 [ "tituloSerie" => "Emerg Infect Dis" "fecha" => "2004" "volumen" => "10" "paginaInicial" => "1074" "paginaFinal" => "1081" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An eight-cysteine-containing CFEM domain unique to a group of fungal membrane proteins" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0968-0004(03)00025-2" "Revista" => array:6 [ "tituloSerie" => "Trends Biochem Sci" "fecha" => "2003" "volumen" => "28" "paginaInicial" => "118" "paginaFinal" => "121" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Novel G-protein-coupled receptor-like proteins in the plant pathogenic fungus Magnaporthe grisea" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/gb-2005-6-3-r24" "Revista" => array:5 [ "tituloSerie" => "Genome Biol" "fecha" => "2005" "volumen" => "6" "paginaInicial" => "R24" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cdk1/Cdc28-dependent activation of the major triacylglycerol lipase Tgl4 in yeast links lipolysis to cell-cycle progression" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.molcel.2008.12.019" "Revista" => array:6 [ "tituloSerie" => "Mol Cell" "fecha" => "2009" "volumen" => "33" "paginaInicial" => "53" "paginaFinal" => "63" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Phenotype switching affects biofilm formation by Candida parapsilosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1099/mic.0.27739-0" "Revista" => array:6 [ "tituloSerie" => "Microbiology" "fecha" => "2005" "volumen" => "151" "paginaInicial" => "1073" "paginaFinal" => "1081" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fatty acid synthesis by elongases in trypanosomes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cell.2006.06.045" "Revista" => array:6 [ "tituloSerie" => "Cell" "fecha" => "2006" "volumen" => "126" "paginaInicial" => "691" "paginaFinal" => "699" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0220" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Emergence of Candida parapsilosis as the predominant species causing candidemia in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "1998" "volumen" => "26" "paginaInicial" => "1086" "paginaFinal" => "1088" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0225" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The genes encoding the secreted aspartyl proteinases of Candida albicans constitute a family with at least three members" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Infect Immun" "fecha" => "1993" "volumen" => "61" "paginaInicial" => "3240" "paginaFinal" => "3243" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0230" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lipid droplets: a unified view of a dynamic organelle" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrm1912" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Mol Cell Biol" "fecha" => "2006" "volumen" => "7" "paginaInicial" => "373" "paginaFinal" => "378" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0235" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Yeasts isolated from blood and catheter in children from a public hospital of Sao Paulo, Brazil" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Mycopathologia" "fecha" => "2002" "volumen" => "154" "paginaInicial" => "63" "paginaFinal" => "69" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0240" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "International surveillance of Candida spp. and Aspergillus spp.: report from the SENTRY Antimicrobial Surveillance Program (2003)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/JCM.44.5.1782-1787.2006" "Revista" => array:6 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "2006" "volumen" => "44" "paginaInicial" => "1782" "paginaFinal" => "1787" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0245" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multiplicity of genes encoding secreted aspartic proteinases in Candida species" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Mol Microbiol" "fecha" => "1994" "volumen" => "13" "paginaInicial" => "357" "paginaFinal" => "368" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0250" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genome-wide transcription profiling of the early phase of biofilm formation by Candida albicans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/EC.4.9.1562-1573.2005" "Revista" => array:6 [ "tituloSerie" => "Eukaryot Cell" "fecha" => "2005" "volumen" => "4" "paginaInicial" => "1562" "paginaFinal" => "1573" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0255" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Candida albicans secreted aspartyl proteinases in virulence and pathogenesis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Microbiol Mol Biol Rev" "fecha" => "2003" "volumen" => "67" "paginaInicial" => "400" "paginaFinal" => "428" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0260" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiological study of Candida infections in blood: susceptibilities of Candida spp. to antifungal agents, and clinical features associated with the candidemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10156-006-0438-y" "Revista" => array:6 [ "tituloSerie" => "J Infect Chemother" "fecha" => "2006" "volumen" => "12" "paginaInicial" => "132" "paginaFinal" => "138" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0265" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The lipase/acyltransferase from Candida parapsilosis: molecular cloning and characterization of purified recombinant enzymes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur J Biochem" "fecha" => "2002" "volumen" => "269" "paginaInicial" => "1734" "paginaFinal" => "1745" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0270" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systemic Candida infection in University hospital 1997–1999: the distribution of Candida biotypes and antifungal susceptibility patterns" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Mycopathologia" "fecha" => "2001" "volumen" => "149" "paginaInicial" => "141" "paginaFinal" => "146" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0275" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhibition of Candida parapsilosis fatty acid synthase (Fas2) induces mitochondrial cell death in serum" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.ppat.1002879" "Revista" => array:5 [ "tituloSerie" => "PLoS Pathog" "fecha" => "2012" "volumen" => "8" "paginaInicial" => "e1002879" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib0280" "etiqueta" => "56" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Candida parapsilosis fat storage-inducing transmembrane (FIT) protein 2 regulates lipid droplet formation and impacts virulence" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.micinf.2011.02.009" "Revista" => array:6 [ "tituloSerie" => "Microbes Infect" "fecha" => "2011" "volumen" => "13" "paginaInicial" => "663" "paginaFinal" => "672" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 56 => array:3 [ "identificador" => "bib0285" "etiqueta" => "57" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lipid droplet formation protects against gluco/lipotoxicity in Candida parapsilosis: an essential role of fatty acid desaturase Ole1" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4161/cc.10.18.16932" "Revista" => array:6 [ "tituloSerie" => "Cell Cycle" "fecha" => "2011" "volumen" => "10" "paginaInicial" => "3159" "paginaFinal" => "3167" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 57 => array:3 [ "identificador" => "bib0290" "etiqueta" => "58" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fatty acid synthase impacts the pathobiology of Candida parapsilosis in vitro and during mammalian infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0008421" "Revista" => array:5 [ "tituloSerie" => "PLoS One" "fecha" => "2009" "volumen" => "4" "paginaInicial" => "e8421" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 58 => array:3 [ "identificador" => "bib0295" "etiqueta" => "59" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of serum concentration on Candida biofilm formation on acrylic surfaces" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Mycoses" "fecha" => "2000" "volumen" => "43" "paginaInicial" => "139" "paginaFinal" => "143" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 59 => array:3 [ "identificador" => "bib0300" "etiqueta" => "60" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Critical role of Bcr1-dependent adhesins in C. albicans biofilm formation in vitro and in vivo" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.ppat.0020063" "Revista" => array:5 [ "tituloSerie" => "PLoS Pathog" "fecha" => "2006" "volumen" => "2" "paginaInicial" => "e63" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 60 => array:3 [ "identificador" => "bib0305" "etiqueta" => "61" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Regulation of cell-surface genes and biofilm formation by the C. albicans transcription factor Bcr1p" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cub.2005.05.047" "Revista" => array:6 [ "tituloSerie" => "Curr Biol" "fecha" => "2005" "volumen" => "15" "paginaInicial" => "1150" "paginaFinal" => "1155" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 61 => array:3 [ "identificador" => "bib0310" "etiqueta" => "62" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetics and genomics of Candida albicans biofilm formation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1462-5822.2006.00761.x" "Revista" => array:6 [ "tituloSerie" => "Cell Microbiol" "fecha" => "2006" "volumen" => "8" "paginaInicial" => "1382" "paginaFinal" => "1391" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 62 => array:3 [ "identificador" => "bib0315" "etiqueta" => "63" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Function of Candida albicans adhesin Hwp1 in biofilm formation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/EC.00194-06" "Revista" => array:6 [ "tituloSerie" => "Eukaryot Cell" "fecha" => "2006" "volumen" => "5" "paginaInicial" => "1604" "paginaFinal" => "1610" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 63 => array:3 [ "identificador" => "bib0320" "etiqueta" => "64" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The DGA1 gene determines a second triglyceride synthetic pathway in yeast" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1074/jbc.M111646200" "Revista" => array:6 [ "tituloSerie" => "J Biol Chem" "fecha" => "2002" "volumen" => "277" "paginaInicial" => "8877" "paginaFinal" => "8881" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 64 => array:3 [ "identificador" => "bib0325" "etiqueta" => "65" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum differentially alters the antifungal properties of echinocandin drugs" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/AAC.01536-06" "Revista" => array:6 [ "tituloSerie" => "Antimicrob Agents Chemother" "fecha" => "2007" "volumen" => "51" "paginaInicial" => "2253" "paginaFinal" => "2256" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 65 => array:3 [ "identificador" => "bib0330" "etiqueta" => "66" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Candida parapsilosis is a significant neonatal pathogen: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Pediatr Infect Dis J" "fecha" => "2013" ] ] ] ] ] ] 66 => array:3 [ "identificador" => "bib0335" "etiqueta" => "67" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adhesion of Candida parapsilosis to epithelial and acrylic surfaces correlates with cell surface hydrophobicity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Mycoses" "fecha" => "2001" "volumen" => "44" "paginaInicial" => "29" "paginaFinal" => "35" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 67 => array:3 [ "identificador" => "bib0340" "etiqueta" => "68" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biofilm formation by Candida albicans mutants for genes coding fungal proteins exhibiting the eight-cysteine-containing CFEM domain" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1567-1364.2006.00131.x" "Revista" => array:6 [ "tituloSerie" => "FEMS Yeast Res" "fecha" => "2006" "volumen" => "6" "paginaInicial" => "1074" "paginaFinal" => "1084" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 68 => array:3 [ "identificador" => "bib0345" "etiqueta" => "69" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of invasive candidiasis: a persistent public health problem" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/CMR.00029-06" "Revista" => array:6 [ "tituloSerie" => "Clin Microbiol Rev" "fecha" => "2007" "volumen" => "20" "paginaInicial" => "133" "paginaFinal" => "163" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 69 => array:3 [ "identificador" => "bib0350" "etiqueta" => "70" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "International surveillance of bloodstream infections due to Candida species: frequency of occurrence and antifungal susceptibilities of isolates collected in 1997 in the United States, Canada, and South America for the SENTRY Program. The SENTRY Participant Group" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "1998" "volumen" => "36" "paginaInicial" => "1886" "paginaFinal" => "1889" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 70 => array:3 [ "identificador" => "bib0355" "etiqueta" => "71" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Candida parapsilosis infection following the electrosurgery procedure" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1529-8019.2010.01386.x" "Revista" => array:6 [ "tituloSerie" => "Dermatol Ther" "fecha" => "2011" "volumen" => "24" "paginaInicial" => "131" "paginaFinal" => "133" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 71 => array:3 [ "identificador" => "bib0360" "etiqueta" => "72" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Synthesis and turnover of non-polar lipids in yeast" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.plipres.2008.01.001" "Revista" => array:6 [ "tituloSerie" => "Prog Lipid Res" "fecha" => "2008" "volumen" => "47" "paginaInicial" => "157" "paginaFinal" => "171" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 72 => array:3 [ "identificador" => "bib0365" "etiqueta" => "73" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The filamentation pathway controlled by the Efg1 regulator protein is required for normal biofilm formation and development in Candida albicans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "FEMS Microbiol Lett" "fecha" => "2002" "volumen" => "214" "paginaInicial" => "95" "paginaFinal" => "100" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 73 => array:3 [ "identificador" => "bib0370" "etiqueta" => "74" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multicenter study of fungemia due to yeasts in Argentina" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Argent Microbiol" "fecha" => "2005" "volumen" => "37" "paginaInicial" => "189" "paginaFinal" => "195" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 74 => array:3 [ "identificador" => "bib0375" "etiqueta" => "75" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Correlation between biofilm formation and the hypoxic response in Candida parapsilosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/EC.00350-08" "Revista" => array:6 [ "tituloSerie" => "Eukaryot Cell" "fecha" => "2009" "volumen" => "8" "paginaInicial" => "550" "paginaFinal" => "559" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 75 => array:3 [ "identificador" => "bib0380" "etiqueta" => "76" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transcriptional response of Candida parapsilosis following exposure to farnesol" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/AAC.01438.06" "Revista" => array:6 [ "tituloSerie" => "Antimicrob Agents Chemother" "fecha" => "2007" "volumen" => "51" "paginaInicial" => "2304" "paginaFinal" => "2312" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 76 => array:3 [ "identificador" => "bib0385" "etiqueta" => "77" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Candida acid proteinases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Med Vet Mycol" "fecha" => "1992" "volumen" => "30" "numero" => "Suppl. 1" "paginaInicial" => "123" "paginaFinal" => "132" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 77 => array:3 [ "identificador" => "bib0390" "etiqueta" => "78" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neonatal Candida parapsilosis outbreak with a high case fatality rate" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Pediatr Infect Dis J" "fecha" => "1995" "volumen" => "14" "paginaInicial" => "776" "paginaFinal" => "781" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 78 => array:3 [ "identificador" => "bib0395" "etiqueta" => "79" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transcriptional response of Candida albicans to hypoxia: linkage of oxygen sensing and Efg1p-regulatory networks" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jmb.2006.06.040" "Revista" => array:6 [ "tituloSerie" => "J Mol Biol" "fecha" => "2006" "volumen" => "361" "paginaInicial" => "399" "paginaFinal" => "411" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 79 => array:3 [ "identificador" => "bib0400" "etiqueta" => "80" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Synthesis of triacylglycerols by the acyl-coenzyme A: diacyl-glycerol acyltransferase Dga1p in lipid particles of the yeast Saccharomyces cerevisiae" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Bacteriol" "fecha" => "2002" "volumen" => "184" "paginaInicial" => "519" "paginaFinal" => "524" ] ] ] ] ] ] 80 => array:3 [ "identificador" => "bib0405" "etiqueta" => "81" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Candida parapsilosis, an emerging fungal pathogen" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/CMR.00013-08" "Revista" => array:6 [ "tituloSerie" => "Clin Microbiol Rev" "fecha" => "2008" "volumen" => "21" "paginaInicial" => "606" "paginaFinal" => "625" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 81 => array:3 [ "identificador" => "bib0410" "etiqueta" => "82" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biofilm production by Candida species and inadequate antifungal therapy as predictors of mortality for patients with candidemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/JCM.00131-07" "Revista" => array:6 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "2007" "volumen" => "45" "paginaInicial" => "1843" "paginaFinal" => "1850" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 82 => array:3 [ "identificador" => "bib0415" "etiqueta" => "83" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Candida parapsilosis: a review of its epidemiology, pathogenesis, clinical aspects, typing and antimicrobial susceptibility" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/10408410903213393" "Revista" => array:6 [ "tituloSerie" => "Crit Rev Microbiol" "fecha" => "2009" "volumen" => "35" "paginaInicial" => "283" "paginaFinal" => "309" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 83 => array:3 [ "identificador" => "bib0420" "etiqueta" => "84" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular mechanisms of necroptosis: an ordered cellular explosion" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrm2970" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Mol Cell Biol" "fecha" => "2010" "volumen" => "11" "paginaInicial" => "700" "paginaFinal" => "714" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 84 => array:3 [ "identificador" => "bib0425" "etiqueta" => "85" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Candida parapsilosis: epidemiology, pathogenicity, clinical manifestations, and antimicrobial susceptibility" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ …1] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "1992" "volumen" => "14" "paginaInicial" => "756" "paginaFinal" => "766" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 85 => array:3 [ "identificador" => "bib0430" "etiqueta" => "86" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Candida parapsilosis fungemia associated with parenteral nutrition and contaminated blood pressure transducers" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "1987" "volumen" => "25" "paginaInicial" => "1029" "paginaFinal" => "1032" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 86 => array:3 [ "identificador" => "bib0435" "etiqueta" => "87" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/421946" "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2004" "volumen" => "39" "paginaInicial" => "309" "paginaFinal" => "317" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 87 => array:3 [ "identificador" => "bib0440" "etiqueta" => "88" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Purification and characterization of secretory proteinase of Candida albicans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Microbiol Immunol" "fecha" => "1992" "volumen" => "36" "paginaInicial" => "637" "paginaFinal" => "641" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 88 => array:3 [ "identificador" => "bib0445" "etiqueta" => "89" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Secreted aspartic proteinase family of Candida tropicalis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/IAI.69.1.405-412.2001" "Revista" => array:6 [ "tituloSerie" => "Infect Immun" "fecha" => "2001" "volumen" => "69" "paginaInicial" => "405" "paginaFinal" => "412" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 89 => array:3 [ "identificador" => "bib0450" "etiqueta" => "90" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Requirement for the Candida albicans FAS2 gene for infection in a rat model of oropharyngeal candidiasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => 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Mycologic Forum

Genetic determinants of virulence – Candida parapsilosis

Determinantes genéticos de la virulencia de Candida parapsilosis

Kumara Singaravelua, Attila Gácserb, Joshua D. Nosanchuka,

Corresponding author

josh.nosanchuk@einstein.yu.edu

Corresponding author.

a Departments of Medicine (Infectious Diseases) and Microbiology & Immunology, Albert Einstein College of Medicine, New York, NY, United States

b Department of Microbiology, University of Szeged, Szeged, Hungary

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        "titulo" => "Determinantes gen&#233;ticos de la virulencia de <span class="elsevierStyleItalic">Candida parapsilosis</span>"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Immunofluorescence microscopy of <span class="elsevierStyleItalic">C&#46; parapsilosis</span> and human macrophages&#46; Red yeast are dead &#40;photo credit to C&#46; Papp and A&#46; G&#225;cser&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Since the late 1970s&#44; fungal infections have increasingly become a significant cause of morbidity and mortality especially among hospitalized and immunosuppressed patients&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">69</span></a><span class="elsevierStyleItalic">Candida</span> species are the fourth most frequent causative agent of blood-stream infections&#44; constituting 8&#8211;15&#37; of hospital-acquired infections&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">87</span></a> In the United States&#44; <span class="elsevierStyleItalic">Candida albicans</span> is the most common pathogen followed by <span class="elsevierStyleItalic">Candida parapsilosis</span> or <span class="elsevierStyleItalic">Candida glabrata</span>&#44; depending on the study&#46; However&#44; <span class="elsevierStyleItalic">C&#46; parapsilosis</span> has become the leading causative agent in some institutions located in Europe&#44; Asia and South America&#44; and it is the <span class="elsevierStyleItalic">Candida</span> species with the largest increase in incidence since 1990&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;6&#44;10&#8211;12&#44;20&#44;36&#44;48&#44;52&#44;54&#44;70&#44;74&#44;81&#44;87</span></a> Of all candidal isolates&#44; <span class="elsevierStyleItalic">C&#46; parapsilosis</span> accounts for 15&#46;5&#37; in North America&#44; 16&#46;3&#37; in Europe and 23&#46;4&#37; in Latin America&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a> In the US&#44; it has been the third most common cause of neonatal sepsis&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">66</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">First isolated in 1928 from a stool specimen and thought to be non-pathogenic&#44;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;86</span></a><span class="elsevierStyleItalic">C&#46; parapsilosis</span> is now recognized as being fairly ubiquitous as it can be isolated from humans as a normal skin commensal as well as from domestic animals&#44; insects&#44; soil and marine environments&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;81&#44;85</span></a> It is now especially well documented as a pathogen that arises from exogenous sources of infection in intravenous drug users and via medical instrumentation &#40;e&#46;g&#46; catheters and hyperalimentation solutions&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#44;81</span></a> In particular&#44; <span class="elsevierStyleItalic">C&#46; parapsilosis</span> is recognized for its ability to cause invasive disease in patients without prior evidence of colonization via horizontal transmission through medical devices including catheters&#44; parenteral nutrition solutions&#44; and the hands of healthcare workers&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a> Invasive disease occurs more often in immunocompromised patients&#44; such as individuals with AIDS&#44; cancer and in patients undergoing gastrointestinal surgical procedures&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a> Other risk factors reported in studies include transplant receipt&#44; antibiotic exposure&#44; ophthalmic irrigating solutions and&#44; especially&#44; low birth weight in premature neonates&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;44&#44;78&#44;85&#44;86</span></a> Clinical manifestations of <span class="elsevierStyleItalic">C&#46; parapsilosis</span> include endocarditis&#44; meningitis&#44; peritonitis&#44; arthritis&#44; endophthalmitis&#44; keratitis&#44; otomycosis&#44; onychomycosis&#44; vulvovaginitis and urinary tract infections&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a> Mortality rates attributed to <span class="elsevierStyleItalic">C&#46; parapsilosis</span> range from 4&#37; to 45&#37;&#44; with an average mortality rate of 28&#46;5&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;11&#44;28&#44;81</span></a> Biofilm producing isolates are associated with outbreaks<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> and significantly higher mortality rates&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">82</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Determinants of virulence for candidal disease include adhesion capability to host surface&#44; ability to switch morphology between yeast and filamentous growth&#44; biofilm formation and secretion of extracellular hydrolytic enzymes such as lipases&#44; phospholipases or secreted aspartyl proteinases&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">51&#44;83</span></a> Conflicting data exist regarding phospholipase activity&#44; with some studies demonstrating their presence in clinical isolates and others their absence&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;16&#44;26&#44;47</span></a> Nevertheless&#44; its role in virulence bears consideration&#46; The development of gene disruption methods to produce mutants has been a pivotal achievement in our capacity to gain insights into the interactions of <span class="elsevierStyleItalic">C&#46; parapsilosis</span> with hosts and host effector cells &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41;&#46; This review will focus on the observations made on specific genes that have so far been characterized and shown to significantly influence these virulence traits&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Gene disruption</span><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">C&#46; parapsilosis</span> has a diploid genome and does not have a described sexual cycle&#46; Genetic analysis was initially limited by the availability of appropriate study tools&#46; The first targeted gene disruption method was developed in 2007<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> based on previously established gene disruption protocols in <span class="elsevierStyleItalic">C&#46; albicans</span>&#46; The first targeted deletion in <span class="elsevierStyleItalic">C&#46; parapsilosis</span> was the disruption of secreted lipases&#46; This efficient gene deletion system was developed utilizing the repeated use of the dominant nourseoethricin marker &#40;caSAT1&#41; and subsequent deletion by FLP-mediated&#44; site-specific recombination&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Applying this technique&#44; the lipase locus in <span class="elsevierStyleItalic">C&#46; parapsilosis</span> containing the adjacent lipase genes <span class="elsevierStyleItalic">CpLIP1</span>&#44; <span class="elsevierStyleItalic">CpLIP2</span> were deleted and <span class="elsevierStyleItalic">CPLIP2</span> reconstructed providing an understanding of the role of lipase activity in virulence&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Lipases</span><p id="par0025" class="elsevierStylePara elsevierViewall">Microbial extracellular lipases are virulence factors in a broad range of bacteria and fungi&#44; including <span class="elsevierStyleItalic">Candida</span> species&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a> So far&#44; 10 lipase genes have been identified in <span class="elsevierStyleItalic">C&#46; albicans</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> and disruption&#44; such as the deletion of <span class="elsevierStyleItalic">LIP8</span>&#44; can significantly affect virulence&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Only two lipase genes have been elucidated in <span class="elsevierStyleItalic">C&#46; parapsilosis</span> &#8211; <span class="elsevierStyleItalic">CpLIP1</span> and <span class="elsevierStyleItalic">CpLIP2</span>&#44; of which only the latter has been demonstrated to code for an active protein&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;53</span></a> Utilizing the described targeted gene deletion method&#44; disruption of these lipase genes provides evidence that they play a role in pathogenesis &#40;i&#41; by the decreased tissue damage seen in the presence of lipase inhibitors&#44; &#40;ii&#41; the decreased ability of <span class="elsevierStyleItalic">CpLIP1</span>-<span class="elsevierStyleItalic">CpLIP2</span> homozygous mutants to form complex biofilms&#44; &#40;iii&#41; requirement for lipid-rich media&#44; &#40;iv&#41; increased susceptibility to phagocytosis by macrophage-like cells&#44; and &#40;v&#41; decreased virulence in comparison to wild-type <span class="elsevierStyleItalic">C&#46; parapsilosis</span> yeast in infections of human oral epithelium or during murine intraperitoneal challenges&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;23</span></a> These observations hold significant clinical relevance since <span class="elsevierStyleItalic">C&#46; parapsilosis</span> infections are particularly more commonly seen in patients receiving lipid-rich total parenteral nutrition and thus lipases may be a potential target for future antifungal agent development&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Secreted aspartyl proteinase &#40;Sap&#41;</span><p id="par0030" class="elsevierStylePara elsevierViewall">Secreted aspartyl proteinase &#40;Sap&#41; genes have been demonstrated in most pathogenic <span class="elsevierStyleItalic">Candida</span> including <span class="elsevierStyleItalic">C&#46; albicans&#44; Candida dubliniensis</span>&#44; <span class="elsevierStyleItalic">Candida tropicalis</span> and <span class="elsevierStyleItalic">C&#46; parapsilosis</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#44;45&#44;49&#44;89</span></a> However&#44; they are notably absent in many non-pathogenic yeasts &#40;e&#46;g&#46; <span class="elsevierStyleItalic">Saccharomyces cerevisiae</span>&#41; suggesting their possible role in virulence&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> Sap isoenzymes have several functions such as &#40;i&#41; digestion of host proteins for provision of nitrogen sources&#44; &#40;ii&#41; degradation of host cell surface structure and intracellular substances promoting tissue adhesion and invasion&#44; and &#40;iii&#41; destruction of cells and molecules of the host immune system such as immunoglobulin G heavy chains&#44; 2-macroglobulin&#44; C3 protein&#44; lactoglobulin&#44; lactoperoxidase&#44; collagen&#44; and fibronectin<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">71&#44;77</span></a> thereby enabling evasion of antimicrobial activity&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> For example&#44; vulvovaginal and skin <span class="elsevierStyleItalic">C&#46; albicans</span> isolates exhibit higher <span class="elsevierStyleItalic">in vitro</span> Sap activity compared to blood isolates&#44; which possibly explains the earlier clearance of fungemia in comparison to sustained skin infection in infection models&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;14&#44;15&#44;88</span></a> To date&#44; ten <span class="elsevierStyleItalic">SAP</span> genes &#40;Sap1p-Sap10p&#41; have been identified in <span class="elsevierStyleItalic">C&#46; albicans</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> Their role in <span class="elsevierStyleItalic">C&#46; parapsilosis</span> was unclear until the recent identification of 2 <span class="elsevierStyleItalic">SAPP1</span> genes&#58; <span class="elsevierStyleItalic">SAPP1a</span> and <span class="elsevierStyleItalic">SAPP1b</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">C&#46; parapsilosis</span> genome database &#40;<a id="intr0005" class="elsevierStyleInterRef" href="http://www.sanger.ac.uk/sequencing/candida/parapsilosis">www&#46;sanger&#46;ac&#46;uk&#47;sequencing&#47;candida&#47;parapsilosis</a>&#41; was used to perform <span class="elsevierStyleItalic">in silico</span> analysis of the <span class="elsevierStyleItalic">SAPP1</span> genes&#46; A 2871 base pair-duplicated upstream &#40;<span class="elsevierStyleItalic">SAPP1a</span>&#41; and downstream &#40;<span class="elsevierStyleItalic">SAPP1b</span>&#41; regions were defined in the genome&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> All 4 alleles of the <span class="elsevierStyleItalic">SAPP1</span> gene were deleted from wild-type &#40;WT&#41; <span class="elsevierStyleItalic">C&#46; parapsilosis</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> Separate homozygous <span class="elsevierStyleItalic">&#916;&#916;sapp1a</span>&#44; <span class="elsevierStyleItalic">&#916;&#916;sapp1b</span> and a double-homozygous mutant <span class="elsevierStyleItalic">&#916;&#916;sapp1a-&#916;&#916;sapp1b</span> were generated&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> Subsequent experiments revealed that in an inducer medium&#44; Sapp1p production was reduced by about 50&#37; in the <span class="elsevierStyleItalic">&#916;&#916;sapp1a</span> and <span class="elsevierStyleItalic">&#916;&#916;sapp1b</span> mutants&#44; but a similar effect was not observed for the <span class="elsevierStyleItalic">SAPP2</span> gene&#46; On the other hand&#44; Sapp2p production was greater in the <span class="elsevierStyleItalic">&#916;&#916;sapp1a-&#916;&#916;sapp1b</span> mutant compared to wild-type yeast&#46; This mutant was also hyper-susceptible to human serum&#44; had decreased proteolytic activity&#44; and decreased capacity to damage host-effector cells&#46; Additionally&#44; there was also greater phagocytosis and killing of the <span class="elsevierStyleItalic">&#916;&#916;sapp1a-&#916;&#916;sapp1b</span> yeasts by both human peripheral blood mononuclear cells &#40;PBMCs&#41; and PBMC-derived macrophages &#40;PBMC-DM&#41;&#46; After phagocytosis&#44; the <span class="elsevierStyleItalic">&#916;&#916;sapp1a-&#916;&#916;sapp1b</span> yeasts induced more frequent phagolysosomal fusion&#44; suggesting a role for Sapp1p in promoting intracellular survival&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> Both the lipase and proteinase genes play a major role in biofilm formation which is the hallmark of both bacterial and fungal organisms involved in device related infection&#46; While the basic characteristics for biofilm formation may be similar among biofilm producing organisms&#44; unique differences exist as well&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Biofilm formation</span><p id="par0040" class="elsevierStylePara elsevierViewall">Colonization and infection due to <span class="elsevierStyleItalic">C&#46; parapsilosis</span> are initiated by the organism&#39;s ability to adhere to host cells and tissues followed by the formation of biofilm on medical devices&#44;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a> which is accomplished in part by cell surface hydrophobicity<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">67</span></a> and slime production&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Compared to <span class="elsevierStyleItalic">C&#46; albicans</span>&#44; <span class="elsevierStyleItalic">C&#46; parapsilosis</span> has a 20&#46;6&#37; greater avidity to buccal epithelial cells and 143&#46;7&#37; increased adhesiveness to acrylic material&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">67</span></a> although smaller studies have shown less significant differences&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a> After adherence&#44; biofilm formation is initiated by the establishment of cellular layers via cell-to-cell contact&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">75</span></a> In <span class="elsevierStyleItalic">C&#46; albicans</span>&#44; after adherence to tissues&#44; the cells transform from yeast to hyphal forms&#44; which appear to be a requirement for a structured biofilm&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;73</span></a> Once the mature biofilm is formed it is covered by an extracellular matrix that renders it less susceptible to antifungal medications&#46; The transcriptional changes that occur during this process have been well studied in <span class="elsevierStyleItalic">C&#46; albicans</span>&#44; which reveal significant increases in the expression of genes that participate in glycolysis&#44; amino acid and lipid metabolism&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;50</span></a><span class="elsevierStyleItalic">C&#46; parapsilosis</span> and <span class="elsevierStyleItalic">C&#46; albicans</span> differ in the nature of the biofilm formed&#46; <span class="elsevierStyleItalic">C&#46; parapsilosis</span> forms smaller and less complex structures&#44;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;37</span></a> possibly because they do not produce hyphae&#46; <span class="elsevierStyleItalic">C&#46; parapsilosis</span> biofilms consist of yeast and pseudohyphal cells&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;23&#44;37</span></a> Of note&#44; pseudohyphal phenotypes can generate more biofilm and exhibit greater invasiveness into agar than strains in yeast forms&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> Similarities exist as well between the two species&#58; biofilms of both are inhibited by exogenous farnesol<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42&#44;76</span></a> and Bcr1 &#40;Biofilm and Cell wall Regulator 1&#41; is a major regulator for both species&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;60&#44;61</span></a></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">BCR1</span><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In vivo</span> rat catheter models have been utilized to describe the role of <span class="elsevierStyleItalic">BCR1</span> in the development of biofilms&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleItalic">BCR1</span> has been demonstrated to be a required fungal transcription factor for the formation of biofilms in both <span class="elsevierStyleItalic">C&#46; albicans</span> and <span class="elsevierStyleItalic">C&#46; parapsilosis</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;60&#44;61</span></a> Deletion of <span class="elsevierStyleItalic">BCR1</span> in either species impairs the ability for biofilm formation&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;61</span></a> In <span class="elsevierStyleItalic">C&#46; albicans&#44; BCR1</span> encodes genes targeting adhesins and cell-wall proteins &#40;<span class="elsevierStyleItalic">ALS1&#44; ALS3&#44; HWP1</span> and <span class="elsevierStyleItalic">RBT5</span>&#41; indicating its role in the early adhesive stages of biofilm formation&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">60&#8211;63</span></a> The effect of Bcr1 on biofilm formation is also thought to be in part secondary to its influence on the expression of CFEM &#40;Common in Fungal Extracellular Membranes&#41; family of proteins&#46; CFEMs were initially identified in <span class="elsevierStyleItalic">Magnaportha grisea</span>&#46; They are similar to epidermal growth factor &#40;EGF&#41; domains that are found in extracellular membrane regions and contain an eight-cysteine domain&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">39&#44;40</span></a> The role of CFEM is likely to act as cell surface receptors &#40;adhesins&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> At least 5 CFEM members have been identified in <span class="elsevierStyleItalic">C&#46; albicans</span>&#58; <span class="elsevierStyleItalic">PGA7</span>&#44; <span class="elsevierStyleItalic">PGA10</span>&#44; <span class="elsevierStyleItalic">RBT5</span>&#44; <span class="elsevierStyleItalic">CSA1</span> and <span class="elsevierStyleItalic">CSA2</span>&#46; Three of them&#44; <span class="elsevierStyleItalic">PGA10</span>&#44; <span class="elsevierStyleItalic">RBT5</span> and <span class="elsevierStyleItalic">CSA1</span>&#44; have been identified as vital for biofilm development&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">68</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">C&#46; parapsilosis</span> has seven CFEM members &#40;<span class="elsevierStyleItalic">CFEM1-CFEM7</span>&#41; including tandem duplicates of orthologs of <span class="elsevierStyleItalic">C&#46; albicans RBT5</span>&#44; <span class="elsevierStyleItalic">PGA10</span> and <span class="elsevierStyleItalic">CSA1</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleItalic">CFEM1-CFEM4</span> are in tandem and syntenic with <span class="elsevierStyleItalic">RBT5</span> and <span class="elsevierStyleItalic">PGA-7</span>&#44; which in <span class="elsevierStyleItalic">C&#46; parapsilosis</span> is postulated to have single gene duplications thereby forming <span class="elsevierStyleItalic">CFEM1&#47;CFEM2</span> and <span class="elsevierStyleItalic">CFEM3&#47;CFEM4</span>&#46; <span class="elsevierStyleItalic">CFEM5-6</span> are orthologous with <span class="elsevierStyleItalic">CSA1</span>&#46; An ortholog of <span class="elsevierStyleItalic">CFEM7</span> has not been identified in the <span class="elsevierStyleItalic">Candida</span> clade and may possibly be specific to <span class="elsevierStyleItalic">C&#46; parapsilosis</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Bcr1 exerts a different influence on the <span class="elsevierStyleItalic">CFEM</span> family in <span class="elsevierStyleItalic">C&#46; parapsilosis</span>&#46; In Bcr1d mutants&#44; one member of each orthologous pair of <span class="elsevierStyleItalic">CFEM2</span>&#44; <span class="elsevierStyleItalic">CFEM3</span> and <span class="elsevierStyleItalic">CFEM6</span> are down regulated&#44; whereas expression of <span class="elsevierStyleItalic">CFEM1</span>&#44; <span class="elsevierStyleItalic">CFEM4</span>&#44; <span class="elsevierStyleItalic">CFEM5</span> and <span class="elsevierStyleItalic">CFEM7</span> is not affected&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Interestingly&#44; <span class="elsevierStyleItalic">CFEM 2&#44; CFEM3</span> or <span class="elsevierStyleItalic">CFEM6</span> do not appear to be a requirement for the formation of biofilms in <span class="elsevierStyleItalic">C&#46; parapsilosis</span>&#46; <span class="elsevierStyleItalic">CFEM2</span> and <span class="elsevierStyleItalic">CFEM3</span> are necessary and <span class="elsevierStyleItalic">CFEM6</span> is partially required for the heme utilization&#46; Global transcriptional profiling of cells in an iron-depleted environment has shown the increased expression of 59 genes and decrease in 89 genes&#46; Increased expression occurred in genes linked with cellular iron ion hemostasis and iron ion transport &#40;<span class="elsevierStyleItalic">FTH1</span>&#44; <span class="elsevierStyleItalic">FRE9</span> and <span class="elsevierStyleItalic">FRE10</span>&#41;&#46; Decreased expression was seen in heme containing and iron sulfur proteins &#40;<span class="elsevierStyleItalic">YHB1</span>&#44; <span class="elsevierStyleItalic">SDH2</span> and <span class="elsevierStyleItalic">ISA1</span>&#41; and all mitochondrial genes&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">RBT1</span><p id="par0055" class="elsevierStylePara elsevierViewall">When <span class="elsevierStyleItalic">C&#46; parapsilosis</span> produces biofilms there is an upregulation of the genes involved in the glycolysis&#44; fatty acid metabolism and ergosterol synthesis&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">75</span></a> These changes are similar to the ones observed when <span class="elsevierStyleItalic">C&#46; albicans</span> cells are grown under hypoxic conditions&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">79</span></a> Although <span class="elsevierStyleItalic">C&#46; parapsilosis</span> does not produce true hyphae&#44; the genome includes a member of the hyphae producing gene family&#44; Hwp1&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">76</span></a> One of the members in this family&#44; the gene <span class="elsevierStyleItalic">RBT1</span> is induced during the production of biofilms and under hypoxia&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">76</span></a> In <span class="elsevierStyleItalic">C&#46; albicans&#44; RBT1</span> is induced during filamentation and mutants have been demonstrated to have decreased virulence in rabbit and mouse cornea models&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;33</span></a> In <span class="elsevierStyleItalic">C&#46; parapsilosis&#44; RBT1</span> knockout isolates produce structurally much thinner biofilms than wild type while the heterozygous strains produce an intermediate thickness biofilm&#46; This suggests that for full and appropriate biofilm development both of the <span class="elsevierStyleItalic">RBT1</span> alleles are required&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">75</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Lipid metabolism</span><p id="par0060" class="elsevierStylePara elsevierViewall">Fatty acid formation is vital for the functioning of organisms in all kingdoms&#46; They are building blocks of cell membranes that are products of cellular biosynthesis and require a complex enzyme system&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> So far&#44; three major fatty acid synthesis systems have been identified&#46; Eukaryotes and advanced prokaryotes &#40;<span class="elsevierStyleItalic">Mycobacterium</span>&#44; <span class="elsevierStyleItalic">Nocardia</span> and <span class="elsevierStyleItalic">Corynebacterium</span>&#41; utilize Type I Fatty Acid synthesis system &#40;<span class="elsevierStyleItalic">FAS1</span>&#41;&#44; most bacteria utilize Type II&#44; and parasites such as <span class="elsevierStyleItalic">Trypanosma</span> and <span class="elsevierStyleItalic">Leishmania</span> use <span class="elsevierStyleItalic">FAS3</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> While similar enzymes are found in the three <span class="elsevierStyleItalic">FAS</span> systems&#44; the organization of the encoding genes may significantly vary&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> In fungal organisms&#44; production of essential fatty acids such as saturated and unsaturated fatty acids is critical for the generation and maintenance of cell membranes&#46; Fatty acid synthase &#40;<span class="elsevierStyleItalic">FAS</span>&#41; and fatty acid desaturase &#40;<span class="elsevierStyleItalic">OLE</span>&#41; are important enzymes in this pathway&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a></p><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Fatty acid synthase</span><p id="par0065" class="elsevierStylePara elsevierViewall">Fungal FAS enzymes initiate the formation of a 2&#44;6-MD heterodacemeric complex including subunits that are encoded by <span class="elsevierStyleItalic">FAS1</span> and <span class="elsevierStyleItalic">FAS2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> These enzymes are therefore critical for normal yeast growth&#44; and disruption of even a single gene can significantly alter the organisms&#8217; physiological phenotype and virulence&#46; Fas2 inhibition has been demonstrated to attenuate pathogenicity of <span class="elsevierStyleItalic">Cryptococcus neoformans</span>&#44; <span class="elsevierStyleItalic">C&#46; parapsilosis</span> and <span class="elsevierStyleItalic">C&#46; albicans</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;90&#44;91</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">C&#46; parapsilosis</span> Fas2 &#40;encoded by <span class="elsevierStyleItalic">CpFAS2</span>&#41; heterozygous&#44; homozygous and reconstituted Fas2 mutants have been generated&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a><span class="elsevierStyleItalic">CpFAS2</span> is required for growth in standard medium and gene expression was repressed in the presence of fatty acids&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> Further&#44; up-regulation of <span class="elsevierStyleItalic">CpFAS2</span> occurred when only glucose was made available as the carbon source&#46; In comparison to a wild type yeast&#44; <span class="elsevierStyleItalic">CpFAS2</span> disruptants had a significant decrease in the concentration of unsaturated fatty acids&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a><span class="elsevierStyleItalic">CpFAS2</span> genes are also necessary for normal biofilm formation&#46; Microarray studies demonstrate that <span class="elsevierStyleItalic">CpFAS2</span> is upregulated during <span class="elsevierStyleItalic">in vitro</span> biofilm formation under hypoxic stress&#46; <span class="elsevierStyleItalic">&#916;fas2</span> strains were shown to have decreased capability for biofilm formation on polystyrene and silicone surfaces&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a><span class="elsevierStyleItalic">CpFAS2</span> also appears to play a vital role in helping the organism survive the fungicidal activity of monocytes such as neutrophils and macrophages&#46; Intracellular survival of <span class="elsevierStyleItalic">CpFAS2</span> disruptants was reduced by 40&#37; when compared with wild type and heterozygous strains with a single <span class="elsevierStyleItalic">FAS2</span> gene&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> This decrease in survival could likely be due to diminished membrane stability&#44; thereby enhancing susceptibility to reactive oxygen species secreted by the macrophages&#46; The <span class="elsevierStyleItalic">&#916;fas2</span> strains demonstrate a leaky phenotype when grown under stress conditions&#46; This action&#44; in combination with defective fatty acid production&#44; alters intracellular viability and proliferation of strains with <span class="elsevierStyleItalic">CpFAS2</span> deletion&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The Fas2 enzyme also appears to be critical for survival of <span class="elsevierStyleItalic">C&#46; parapsilosis</span> in serum&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> This is a vital process in fungal pathogenesis as exposure to serum influences virulence traits such as filamentation and biofilm formation&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a> Efficacy of antifungal drugs is decreased in serum&#44; making the eradication of systemic infections difficult&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">65</span></a><span class="elsevierStyleItalic">CpFAS2</span> disruptants are hypersensitive to serum and induce cell death&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> Cell survival also appears to be influenced by the presence of glucose&#44; which causes mitochondria-dependent cell death&#46; Mechanisms of glucose toxicity in <span class="elsevierStyleItalic">&#916;fas2</span> strains are yet unclear&#44; as glucose is usually a preferred carbon source for normal yeast growth&#46; Toxicity may potentially be secondary to uncontrolled metabolism of glucose by the mutant cells&#44; thereby creating an imbalance of cellular contents and subsequent triggering of a cell death response&#44;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> especially via energy-requiring apoptosis pathways&#44; overproduction of ROS&#44; nuclear fragmentation and cell shrinkage&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;84</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Fatty acid desaturase &#40;<span class="elsevierStyleItalic">OLE1</span>&#41;</span><p id="par0080" class="elsevierStylePara elsevierViewall">In addition to glucotoxicity&#44; elevated lipid content is thought to be detrimental to normal yeast growth&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> In <span class="elsevierStyleItalic">C&#46; parapsilosis</span>&#44; exposure to high glucose induces formation of lipid droplets &#40;LD&#41;&#59; it is considered a possible mechanism through which yeast cells survive gluco- and lipo-toxicity&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> Both the <span class="elsevierStyleItalic">CpFAS2</span> and fatty acid desaturase genes &#40;<span class="elsevierStyleItalic">OLE1</span>&#41; appear to play a role&#46; Disruption of either of these genes inhibits LD formation from glucose&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> Moreover&#44; <span class="elsevierStyleItalic">OLE1</span> inhibition resulted in gluco&#47;lipotoxicity of log phage yeast cells&#46; While survival of wild type yeasts was decreased after 2 days of incubation&#44; <span class="elsevierStyleItalic">&#916;ole1</span> mutants died within a few hours of incubation&#44; indicating its role in glucose detoxification&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> In addition to glucose&#44; <span class="elsevierStyleItalic">OLE1</span> deletion strains are also hypersusceptible to fructose&#44; galactose&#44; and mannose&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">FIT2</span><p id="par0085" class="elsevierStylePara elsevierViewall">Lipid droplets &#40;LDs&#41; are cytoplasmic compartments that contain triacylglycerides &#40;TAGs&#41; that serve as fatty acid reservoirs<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> and lipid precursors of fatty acids &#40;FA&#41; and diacyl glycerol &#40;DAG&#41; for membrane lipids such as glycerophospholipids and sphingolipids&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;41</span></a> TAGs and steryl esters are major components of LDs and utilize fatty acyl CoA as a common substrate&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">72</span></a> Akin to mammalian cells&#44; LDs may significantly influence the functioning of pathogenic fungi&#46; In <span class="elsevierStyleItalic">C&#46; parapsilosis</span>&#44; formation of LDs is necessary for normal cell growth and virulence&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a> A family of proteins involved in LD formation &#8211; fat storage-inducing transmembrane proteins 1 and 2 &#40;<span class="elsevierStyleItalic">FIT1</span> and <span class="elsevierStyleItalic">FIT2</span>&#41; &#8211; has recently been demonstrated in both humans and mice&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">35&#44;56</span></a> In mammalian cells&#44; <span class="elsevierStyleItalic">FIT2</span> orthologs enable compartmentalization of TAG in LDs and depleting <span class="elsevierStyleItalic">FIT2</span> transcripts in adipocytes decreased LD formation&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> The <span class="elsevierStyleItalic">FIT2</span> proteins are primarily localized to the endoplasmic reticulum and are responsible for lipid partitioning rather than lipid synthesis&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> Effects of <span class="elsevierStyleItalic">FIT2</span> on LD accumulation are therefore likely downstream in comparison to the DGA1 pathway&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">64&#44;80</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">In <span class="elsevierStyleItalic">C&#46; parapsilosis</span>&#44; disruption of <span class="elsevierStyleItalic">FIT2</span> impairs LD formation&#44; alters the lipidome and attenuates virulence&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a> Both <span class="elsevierStyleItalic">in vitro</span> and <span class="elsevierStyleItalic">in vivo</span> studies demonstrated that heterozygous strains with deletion of one <span class="elsevierStyleItalic">FIT2</span> allele did not decrease TAG formation or LD size&#46; However&#44; deletion of both <span class="elsevierStyleItalic">FIT2</span> alleles significantly decreased TAG content &#40;39&#37;&#41; and LD accumulation&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a> Alterations were also noted in other lipid species with <span class="elsevierStyleItalic">FIT2</span> deletion&#46; While a 25&#37; reduction was observed in fatty acids &#40;FFA&#41;&#44; unsaturated fatty oleic &#40;4&#46;63&#37;&#41; and linoleic acids &#40;12&#46;31&#37;&#41;&#44; elevations were noted in steryl esters &#40;135&#37;&#41;&#44; diacylglycerols&#47;sterols &#40;96&#37;&#41; and phospholipids &#40;112&#37;&#41;&#44; palmitic &#40;1&#46;5&#37;&#41; and stearic acids &#40;15&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a> However&#44; <span class="elsevierStyleItalic">FIT2</span> deletion did not alter susceptibility to standard antifungal drugs&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conclusions</span><p id="par0095" class="elsevierStylePara elsevierViewall">The epidemiology of microorganisms that impact human morbidity and mortality is constantly evolving&#46; Globally&#44; there is increased life expectancy&#44; improved and more frequent access to the healthcare system&#44; rising use of immunosuppressants&#44; immunomodulators and biologics&#44; and increased utilization of indwelling devices such as catheters and cardiovascular devices&#46; Microbes that have the ability to evade the host immune system&#44; produce biofilms and develop resistance to available treatment options have and will significantly impact morbidity and mortality&#46; This is well exemplified by the globally increasing prevalence of <span class="elsevierStyleItalic">C&#46; parapsilosis</span> infections&#46; A significant work has been accomplished in identifying the genetic factors that determine the organism&#39;s virulence&#44; and increased efforts are urgently needed to counter this global threat&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflict of interests</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Abstract"
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          "titulo" => "Gene disruption"
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          "identificador" => "sec0010"
          "titulo" => "Lipases"
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        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Secreted aspartyl proteinase &#40;Sap&#41;"
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        7 => array:3 [
          "identificador" => "sec0020"
          "titulo" => "Biofilm formation"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "BCR1"
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            1 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "RBT1"
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          "identificador" => "sec0035"
          "titulo" => "Lipid metabolism"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Fatty acid synthase"
            ]
            1 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Fatty acid desaturase &#40;OLE1&#41;"
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            2 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "FIT2"
            ]
          ]
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        9 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Conclusions"
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        10 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Conflict of interests"
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          "identificador" => "xack73815"
          "titulo" => "Acknowledgements"
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          "titulo" => "References"
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    "fechaRecibido" => "2013-08-15"
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          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec294362"
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            0 => "<span class="elsevierStyleItalic">Candida parapsilosis</span>"
            1 => "Gene disruption"
            2 => "Lipase"
            3 => "Secreted aspartyl proteinases"
            4 => "Phospholipase"
            5 => "Fatty acid biosynthesis"
            6 => "Biofilm"
            7 => "Virulence"
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          "identificador" => "xpalclavsec294361"
          "palabras" => array:8 [
            0 => "<span class="elsevierStyleItalic">Candida parapsilosis</span>"
            1 => "Alteraci&#243;n g&#233;nica"
            2 => "Lipasa"
            3 => "Secreci&#243;n de aspartilproteinasas"
            4 => "Fosfolipasa"
            5 => "Bios&#237;ntesis de &#225;cidos grasos"
            6 => "Biopel&#237;cula"
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        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The global epidemiology of fungal infections is changing&#46; While overall&#44; <span class="elsevierStyleItalic">Candida albicans</span> remains the most common pathogen&#59; several institutions in Europe&#44; Asia and South America have reported the rapid emergence to predominance of <span class="elsevierStyleItalic">Candida parapsilosis&#46;</span> This mini-review examines the impact of gene deletions achieved in <span class="elsevierStyleItalic">C&#46; parapsilosis</span> that have been published to date&#46; The molecular approaches to gene disruption in <span class="elsevierStyleItalic">C&#46; parapsilosis</span> and the molecularly characterized genes to date are reviewed&#46; Similar to <span class="elsevierStyleItalic">C&#46; albicans</span>&#44; factors influencing virulence in <span class="elsevierStyleItalic">C&#46; parapsilosis</span> include adherence&#44; biofilm formation&#44; lipid metabolism&#44; and secretion of hydrolytic enzymes such as lipases&#44; phospholipases and secreted aspartyl proteinases&#46; Development of a targeted gene deletion method has enabled the identification of several unique aspects of <span class="elsevierStyleItalic">C&#46; parapsilosis</span> genes that play a role in host&#8211;pathogen interactions &#8211; CpLIP1&#44; CpLIP2&#44; SAPP1a&#44; SAPP1b&#44; BCR1&#44; RBT1&#44; CpFAS2&#44; OLE1&#44; FIT-2&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This manuscript is part of the series of works presented at the &#8220;V International Workshop&#58; Molecular genetic approaches to the study of human pathogenic fungi&#8221; &#40;Oaxaca&#44; Mexico&#44; 2012&#41;&#46;</p>"
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:91 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology&#44; risk factors&#44; and prognosis of <span class="elsevierStyleItalic">Candida parapsilosis</span> bloodstream infections&#58; case-control population-based surveillance study of patients in Barcelona&#44; Spain&#44; from 2002 to 2003"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Almirante"
                            1 => "D&#46; Rodriguez"
                            2 => "M&#46; Cuenca-Estrella"
                            3 => "M&#46; Almela"
                            4 => "F&#46; Sanchez"
                            5 => "J&#46; Ayats"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/JCM.44.5.1681-1685.2006"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Microbiol"
                        "fecha" => "2006"
                        "volumen" => "44"
                        "paginaInicial" => "1681"
                        "paginaFinal" => "1685"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16672393"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Certain conditions of the gastrointestinal tract in Puerto Rico and their relation to tropical sprue"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "B&#46; Ashford"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Trop Med Hyg"
                        "fecha" => "1928"
                        "volumen" => "8"
                        "paginaInicial" => "507"
                        "paginaFinal" => "538"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of dimorphism in the development of <span class="elsevierStyleItalic">Candida albicans</span> biofilms"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G&#46;S&#46; Baillie"
                            1 => "L&#46;J&#46; Douglas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1099/00222615-48-7-671"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Med Microbiol"
                        "fecha" => "1999"
                        "volumen" => "48"
                        "paginaInicial" => "671"
                        "paginaFinal" => "679"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10403418"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genotypic variation and slime production among blood and catheter isolates of <span class="elsevierStyleItalic">Candida parapsilosis</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46;L&#46; Branchini"
                            1 => "M&#46;A&#46; Pfaller"
                            2 => "J&#46; Rhine-Chalberg"
                            3 => "T&#46; Frempong"
                            4 => "H&#46;D&#46; Isenberg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Clin Microbiol"
                        "fecha" => "1994"
                        "volumen" => "32"
                        "paginaInicial" => "452"
                        "paginaFinal" => "456"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Identification and characterization of TUP1-regulated genes in <span class="elsevierStyleItalic">Candida albicans</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "B&#46;R&#46; Braun"
                            1 => "W&#46;S&#46; Head"
                            2 => "M&#46;X&#46; Wang"
                            3 => "A&#46;D&#46; Johnson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Genetics"
                        "fecha" => "2000"
                        "volumen" => "156"
                        "paginaInicial" => "31"
                        "paginaFinal" => "44"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical and microbiological aspects of candidemia due to <span class="elsevierStyleItalic">Candida parapsilosis</span> in Brazilian tertiary care hospitals"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;R&#46; Brito"
                            1 => "T&#46; Guimaraes"
                            2 => "M&#46; Nucci"
                            3 => "R&#46;C&#46; Rosas"
                            4 => "L&#46; Paula Almeida"
                            5 => "D&#46;A&#46; Da Matta"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/13693780500421476"
                      "Revista" => array:6 [
                        "tituloSerie" => "Med Mycol"
                        "fecha" => "2006"
                        "volumen" => "44"
                        "paginaInicial" => "261"
                        "paginaFinal" => "266"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16702106"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High-level expression of <span class="elsevierStyleItalic">Candida parapsilosis</span> lipase&#47;acyltransferase in <span class="elsevierStyleItalic">Pichia pastoris</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Brunel"
                            1 => "V&#46; Neugnot"
                            2 => "L&#46; Landucci"
                            3 => "H&#46; Boze"
                            4 => "G&#46; Moulin"
                            5 => "F&#46; Bigey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jbiotec.2004.03.007"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biotechnol"
                        "fecha" => "2004"
                        "volumen" => "111"
                        "paginaInicial" => "41"
                        "paginaFinal" => "50"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15196768"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biotype diversity of <span class="elsevierStyleItalic">Candida parapsilosis</span> and its relationship to the clinical source and experimental pathogenicity"
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                        0 => array:2 [
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                          "autores" => array:6 [
                            0 => "A&#46; Cassone"
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                            2 => "E&#46; Pontieri"
                            3 => "G&#46; Carruba"
                            4 => "C&#46; Girmenia"
                            5 => "P&#46; Martino"
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                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Infect Dis"
                        "fecha" => "1995"
                        "volumen" => "171"
                        "paginaInicial" => "967"
                        "paginaFinal" => "975"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7706826"
                            "web" => "Medline"
                          ]
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                    ]
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                ]
              ]
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              "identificador" => "bib0045"
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                    0 => array:2 [
                      "titulo" => "Fatty acid synthesis is essential for survival of <span class="elsevierStyleItalic">Cryptococcus neoformans</span> and a potential fungicidal target"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Chayakulkeeree"
                            1 => "T&#46;H&#46; Rude"
                            2 => "D&#46;L&#46; Toffaletti"
                            3 => "J&#46;R&#46; Perfect"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/AAC.00442-07"
                      "Revista" => array:6 [
                        "tituloSerie" => "Antimicrob Agents Chemother"
                        "fecha" => "2007"
                        "volumen" => "51"
                        "paginaInicial" => "3537"
                        "paginaFinal" => "3545"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17698629"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Prospective observational study of candidemia in Sao Paulo&#44; Brazil&#58; incidence rate&#44; epidemiology&#44; and predictors of mortality"
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                            0 => "A&#46;L&#46; Colombo"
                            1 => "T&#46; Guimaraes"
                            2 => "L&#46;R&#46; Silva"
                            3 => "L&#46;P&#46; de Almeida Monfardini"
                            4 => "A&#46;K&#46; Cunha"
                            5 => "P&#46; Rady"
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                  "host" => array:1 [
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                      "doi" => "10.1086/513615"
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                        "tituloSerie" => "Infect Control Hosp Epidemiol"
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                        "volumen" => "28"
                        "paginaInicial" => "570"
                        "paginaFinal" => "576"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17464917"
                            "web" => "Medline"
                          ]
                        ]
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                  ]
                ]
              ]
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            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology of candidemia in Brazil&#58; a nationwide sentinel surveillance of candidemia in eleven medical centers"
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                            1 => "M&#46; Nucci"
                            2 => "B&#46;J&#46; Park"
                            3 => "S&#46;A&#46; Nouer"
                            4 => "B&#46; Arthington-Skaggs"
                            5 => "D&#46;A&#46; da Matta"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/JCM.00773-06"
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                        "tituloSerie" => "J Clin Microbiol"
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                        "volumen" => "44"
                        "paginaInicial" => "2816"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16891497"
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              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A first Portuguese epidemiological survey of fungaemia in a university hospital"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46; Costa-de-Oliveira"
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                            2 => "D&#46; Mendonca"
                            3 => "A&#46; Goncalves Rodrigues"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10096-007-0448-4"
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                        "tituloSerie" => "Eur J Clin Microbiol Infect Dis"
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                        "volumen" => "27"
                        "paginaInicial" => "365"
                        "paginaFinal" => "374"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18204871"
                            "web" => "Medline"
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                  ]
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            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Synthesis&#44; storage and degradation of neutral lipids in yeast"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "T&#46; Czabany"
                            1 => "K&#46; Athenstaedt"
                            2 => "G&#46; Daum"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbalip.2006.07.001"
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                        "tituloSerie" => "Biochim Biophys Acta"
                        "fecha" => "2007"
                        "volumen" => "1771"
                        "paginaInicial" => "299"
                        "paginaFinal" => "309"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16916618"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acid proteinase&#44; phospholipase and adherence properties of <span class="elsevierStyleItalic">Candida parapsilosis</span> strains isolated from clinical specimens of hospitalised patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46; Dagdeviren"
                            1 => "N&#46; Cerikcioglu"
                            2 => "M&#46; Karavus"
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                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "doi" => "10.1111/j.1439-0507.2005.01145.x"
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                        "tituloSerie" => "Mycoses"
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                        "volumen" => "48"
                        "paginaInicial" => "321"
                        "paginaFinal" => "326"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16115102"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Biotyping and virulence properties of skin isolates of <span class="elsevierStyleItalic">Candida parapsilosis</span>"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
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                            1 => "F&#46; Mondello"
                            2 => "R&#46; San Millan"
                            3 => "J&#46; Ponton"
                            4 => "A&#46; Cassone"
                          ]
                        ]
                      ]
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                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Microbiol"
                        "fecha" => "1999"
                        "volumen" => "37"
                        "paginaInicial" => "3481"
                        "paginaFinal" => "3486"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10523538"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">In vitro</span> differential activity of phospholipases and acid proteinases of clinical isolates of <span class="elsevierStyleItalic">Candida</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; D&#8217;Eca Junior"
                            1 => "A&#46;F&#46; Silva"
                            2 => "F&#46;C&#46; Rosa"
                            3 => "S&#46;G&#46; Monteiro"
                            4 => "P&#46; de Maria Silva Figueiredo"
                            5 => "C&#46; de Andrade Monteiro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Soc Bras Med Trop"
                        "fecha" => "2011"
                        "volumen" => "44"
                        "paginaInicial" => "334"
                        "paginaFinal" => "338"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21901875"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Development of a gene knockout system in <span class="elsevierStyleItalic">Candida parapsilosis</span> reveals a conserved role for BCR1 in biofilm formation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/EC.00136-07"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eukaryot Cell"
                        "fecha" => "2007"
                        "volumen" => "6"
                        "paginaInicial" => "1310"
                        "paginaFinal" => "1319"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Conserved and divergent roles of Bcr1 and CFEM proteins in <span class="elsevierStyleItalic">Candida parapsilosis</span> and <span class="elsevierStyleItalic">Candida albicans</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0028151"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS One"
                        "fecha" => "2011"
                        "volumen" => "6"
                        "paginaInicial" => "e28151"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Systematics of yeast species in the <span class="elsevierStyleItalic">Candida parapsilosis</span> group"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Mycopathol Mycol Appl"
                        "fecha" => "1967"
                        "volumen" => "32"
                        "paginaInicial" => "177"
                        "paginaFinal" => "193"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Changing incidence of <span class="elsevierStyleItalic">Candida</span> bloodstream infections among NICU patients in the United States&#58; 1995&#8211;2004"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1542/peds.2005-1996"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatrics"
                        "fecha" => "2006"
                        "volumen" => "117"
                        "paginaInicial" => "1680"
                        "paginaFinal" => "1687"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Virulence of <span class="elsevierStyleItalic">Candida parapsilosis</span>&#44; <span class="elsevierStyleItalic">Candida orthopsilosis</span>&#44; and <span class="elsevierStyleItalic">Candida metapsilosis</span> in reconstituted human tissue models"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.fgb.2007.02.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Fungal Genet Biol"
                        "fecha" => "2007"
                        "volumen" => "44"
                        "paginaInicial" => "1336"
                        "paginaFinal" => "1341"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lipase 8 affects the pathogenesis of <span class="elsevierStyleItalic">Candida albicans</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Infect Immun"
                        "fecha" => "2007"
                        "volumen" => "75"
                        "paginaInicial" => "4710"
                        "paginaFinal" => "4718"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Targeted gene deletion in <span class="elsevierStyleItalic">Candida parapsilosis</span> demonstrates the role of secreted lipase in virulence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2007"
                        "volumen" => "117"
                        "paginaInicial" => "3049"
                        "paginaFinal" => "3058"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Candida albicans</span> biofilms&#58; a developmental state associated with specific and stable gene expression patterns"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eukaryot Cell"
                        "fecha" => "2004"
                        "volumen" => "3"
                        "paginaInicial" => "536"
                        "paginaFinal" => "545"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Candida dubliniensis</span>&#58; phylogeny and putative virulence factors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1099/00221287-144-4-829"
                      "Revista" => array:6 [
                        "tituloSerie" => "Microbiology"
                        "fecha" => "1998"
                        "volumen" => "144"
                        "paginaInicial" => "829"
                        "paginaFinal" => "838"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acid proteinase&#44; phospholipase&#44; and biofilm production of <span class="elsevierStyleItalic">Candida</span> species isolated from blood cultures"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s11046-007-9053-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mycopathologia"
                        "fecha" => "2007"
                        "volumen" => "164"
                        "paginaInicial" => "265"
                        "paginaFinal" => "269"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sugar-induced apoptosis in yeast cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "FEMS Yeast Res"
                        "fecha" => "2003"
                        "volumen" => "4"
                        "paginaInicial" => "7"
                        "paginaFinal" => "13"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Attributable mortality of nosocomial candidemia&#44; revisited"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1086/378745"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Infect Dis"
                        "fecha" => "2003"
                        "volumen" => "37"
                        "paginaInicial" => "1172"
                        "paginaFinal" => "1177"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biofilm formation by <span class="elsevierStyleItalic">Candida</span> species on the surface of catheter materials in vitro"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Infect Immun"
                        "fecha" => "1994"
                        "volumen" => "62"
                        "paginaInicial" => "915"
                        "paginaFinal" => "921"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The identification of gene duplication and the role of secreted aspartyl proteinase 1 in <span class="elsevierStyleItalic">Candida parapsilosis</span> virulence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/infdis/jir873"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Infect Dis"
                        "fecha" => "2012"
                        "volumen" => "205"
                        "paginaInicial" => "923"
                        "paginaFinal" => "933"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Candida albicans</span> proteinases&#58; resolving the mystery of a gene family"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1099/00221287-147-8-1997"
                      "Revista" => array:6 [
                        "tituloSerie" => "Microbiology"
                        "fecha" => "2001"
                        "volumen" => "147"
                        "paginaInicial" => "1997"
                        "paginaFinal" => "2005"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Secreted lipases of <span class="elsevierStyleItalic">Candida albicans</span>&#58; cloning&#44; characterisation and expression analysis of a new gene family with at least ten members"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Microbiol"
                        "fecha" => "2000"
                        "volumen" => "174"
                        "paginaInicial" => "362"
                        "paginaFinal" => "374"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Corneal virulence of <span class="elsevierStyleItalic">Candida albicans</span> strains deficient in Tup1-regulated genes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Invest Ophthalmol Vis Sci"
                        "fecha" => "2007"
                        "volumen" => "48"
                        "paginaInicial" => "2535"
                        "paginaFinal" => "2539"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Subacute endocarditis and systemic mycosis &#40;monilia&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "1940"
                        "volumen" => "115"
                        "paginaInicial" => "205"
                        "paginaFinal" => "208"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evolutionarily conserved gene family important for fat storage"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.0708579105"
                      "Revista" => array:6 [
                        "tituloSerie" => "Proc Natl Acad Sci USA"
                        "fecha" => "2008"
                        "volumen" => "105"
                        "paginaInicial" => "94"
                        "paginaFinal" => "99"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fungemia in neonates&#58; report of 80 cases from seven University hospitals"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatrics"
                        "fecha" => "2000"
                        "volumen" => "105"
                        "paginaInicial" => "913"
                        "paginaFinal" => "914"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of biofilms formed by <span class="elsevierStyleItalic">Candida albicans</span> and <span class="elsevierStyleItalic">Candida parapsilosis</span> on bioprosthetic surfaces"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Infect Immun"
                        "fecha" => "2002"
                        "volumen" => "70"
                        "paginaInicial" => "878"
                        "paginaFinal" => "888"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Candida parapsilosis</span> characterization in an outbreak setting"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3201/eid1006.030873"
                      "Revista" => array:6 [
                        "tituloSerie" => "Emerg Infect Dis"
                        "fecha" => "2004"
                        "volumen" => "10"
                        "paginaInicial" => "1074"
                        "paginaFinal" => "1081"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An eight-cysteine-containing CFEM domain unique to a group of fungal membrane proteins"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0968-0004(03)00025-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Trends Biochem Sci"
                        "fecha" => "2003"
                        "volumen" => "28"
                        "paginaInicial" => "118"
                        "paginaFinal" => "121"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Novel G-protein-coupled receptor-like proteins in the plant pathogenic fungus <span class="elsevierStyleItalic">Magnaporthe grisea</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/gb-2005-6-3-r24"
                      "Revista" => array:5 [
                        "tituloSerie" => "Genome Biol"
                        "fecha" => "2005"
                        "volumen" => "6"
                        "paginaInicial" => "R24"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cdk1&#47;Cdc28-dependent activation of the major triacylglycerol lipase Tgl4 in yeast links lipolysis to cell-cycle progression"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.molcel.2008.12.019"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Cell"
                        "fecha" => "2009"
                        "volumen" => "33"
                        "paginaInicial" => "53"
                        "paginaFinal" => "63"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Phenotype switching affects biofilm formation by <span class="elsevierStyleItalic">Candida parapsilosis</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1099/mic.0.27739-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Microbiology"
                        "fecha" => "2005"
                        "volumen" => "151"
                        "paginaInicial" => "1073"
                        "paginaFinal" => "1081"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fatty acid synthesis by elongases in trypanosomes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cell.2006.06.045"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell"
                        "fecha" => "2006"
                        "volumen" => "126"
                        "paginaInicial" => "691"
                        "paginaFinal" => "699"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Emergence of <span class="elsevierStyleItalic">Candida parapsilosis</span> as the predominant species causing candidemia in children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Infect Dis"
                        "fecha" => "1998"
                        "volumen" => "26"
                        "paginaInicial" => "1086"
                        "paginaFinal" => "1088"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The genes encoding the secreted aspartyl proteinases of <span class="elsevierStyleItalic">Candida albicans</span> constitute a family with at least three members"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Infect Immun"
                        "fecha" => "1993"
                        "volumen" => "61"
                        "paginaInicial" => "3240"
                        "paginaFinal" => "3243"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lipid droplets&#58; a unified view of a dynamic organelle"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrm1912"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Mol Cell Biol"
                        "fecha" => "2006"
                        "volumen" => "7"
                        "paginaInicial" => "373"
                        "paginaFinal" => "378"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Yeasts isolated from blood and catheter in children from a public hospital of Sao Paulo&#44; Brazil"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Mycopathologia"
                        "fecha" => "2002"
                        "volumen" => "154"
                        "paginaInicial" => "63"
                        "paginaFinal" => "69"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "International surveillance of <span class="elsevierStyleItalic">Candida</span> spp&#46; and <span class="elsevierStyleItalic">Aspergillus</span> spp&#46;&#58; report from the SENTRY Antimicrobial Surveillance Program &#40;2003&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/JCM.44.5.1782-1787.2006"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Microbiol"
                        "fecha" => "2006"
                        "volumen" => "44"
                        "paginaInicial" => "1782"
                        "paginaFinal" => "1787"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Multiplicity of genes encoding secreted aspartic proteinases in <span class="elsevierStyleItalic">Candida</span> species"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Microbiol"
                        "fecha" => "1994"
                        "volumen" => "13"
                        "paginaInicial" => "357"
                        "paginaFinal" => "368"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genome-wide transcription profiling of the early phase of biofilm formation by <span class="elsevierStyleItalic">Candida albicans</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/EC.4.9.1562-1573.2005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eukaryot Cell"
                        "fecha" => "2005"
                        "volumen" => "4"
                        "paginaInicial" => "1562"
                        "paginaFinal" => "1573"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Candida albicans</span> secreted aspartyl proteinases in virulence and pathogenesis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Microbiol Mol Biol Rev"
                        "fecha" => "2003"
                        "volumen" => "67"
                        "paginaInicial" => "400"
                        "paginaFinal" => "428"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiological study of <span class="elsevierStyleItalic">Candida</span> infections in blood&#58; susceptibilities of <span class="elsevierStyleItalic">Candida</span> spp&#46; to antifungal agents&#44; and clinical features associated with the candidemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10156-006-0438-y"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Infect Chemother"
                        "fecha" => "2006"
                        "volumen" => "12"
                        "paginaInicial" => "132"
                        "paginaFinal" => "138"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The lipase&#47;acyltransferase from <span class="elsevierStyleItalic">Candida parapsilosis</span>&#58; molecular cloning and characterization of purified recombinant enzymes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Biochem"
                        "fecha" => "2002"
                        "volumen" => "269"
                        "paginaInicial" => "1734"
                        "paginaFinal" => "1745"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Systemic <span class="elsevierStyleItalic">Candida</span> infection in University hospital 1997&#8211;1999&#58; the distribution of <span class="elsevierStyleItalic">Candida</span> biotypes and antifungal susceptibility patterns"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Mycopathologia"
                        "fecha" => "2001"
                        "volumen" => "149"
                        "paginaInicial" => "141"
                        "paginaFinal" => "146"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhibition of <span class="elsevierStyleItalic">Candida parapsilosis</span> fatty acid synthase &#40;Fas2&#41; induces mitochondrial cell death in serum"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.ppat.1002879"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS Pathog"
                        "fecha" => "2012"
                        "volumen" => "8"
                        "paginaInicial" => "e1002879"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Candida parapsilosis</span> fat storage-inducing transmembrane &#40;FIT&#41; protein 2 regulates lipid droplet formation and impacts virulence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.micinf.2011.02.009"
                      "Revista" => array:6 [
                        "tituloSerie" => "Microbes Infect"
                        "fecha" => "2011"
                        "volumen" => "13"
                        "paginaInicial" => "663"
                        "paginaFinal" => "672"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lipid droplet formation protects against gluco&#47;lipotoxicity in <span class="elsevierStyleItalic">Candida parapsilosis</span>&#58; an essential role of fatty acid desaturase Ole1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4161/cc.10.18.16932"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell Cycle"
                        "fecha" => "2011"
                        "volumen" => "10"
                        "paginaInicial" => "3159"
                        "paginaFinal" => "3167"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fatty acid synthase impacts the pathobiology of <span class="elsevierStyleItalic">Candida parapsilosis</span> in vitro and during mammalian infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0008421"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS One"
                        "fecha" => "2009"
                        "volumen" => "4"
                        "paginaInicial" => "e8421"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of serum concentration on <span class="elsevierStyleItalic">Candida</span> biofilm formation on acrylic surfaces"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Mycoses"
                        "fecha" => "2000"
                        "volumen" => "43"
                        "paginaInicial" => "139"
                        "paginaFinal" => "143"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Critical role of Bcr1-dependent adhesins in <span class="elsevierStyleItalic">C&#46; albicans</span> biofilm formation in vitro and in vivo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.ppat.0020063"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS Pathog"
                        "fecha" => "2006"
                        "volumen" => "2"
                        "paginaInicial" => "e63"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regulation of cell-surface genes and biofilm formation by the <span class="elsevierStyleItalic">C&#46; albicans</span> transcription factor Bcr1p"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cub.2005.05.047"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Biol"
                        "fecha" => "2005"
                        "volumen" => "15"
                        "paginaInicial" => "1150"
                        "paginaFinal" => "1155"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genetics and genomics of <span class="elsevierStyleItalic">Candida albicans</span> biofilm formation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1462-5822.2006.00761.x"
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                        "tituloSerie" => "Cell Microbiol"
                        "fecha" => "2006"
                        "volumen" => "8"
                        "paginaInicial" => "1382"
                        "paginaFinal" => "1391"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            62 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Function of <span class="elsevierStyleItalic">Candida albicans</span> adhesin Hwp1 in biofilm formation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/EC.00194-06"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eukaryot Cell"
                        "fecha" => "2006"
                        "volumen" => "5"
                        "paginaInicial" => "1604"
                        "paginaFinal" => "1610"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The DGA1 gene determines a second triglyceride synthetic pathway in yeast"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.M111646200"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "2002"
                        "volumen" => "277"
                        "paginaInicial" => "8877"
                        "paginaFinal" => "8881"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Serum differentially alters the antifungal properties of echinocandin drugs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/AAC.01536-06"
                      "Revista" => array:6 [
                        "tituloSerie" => "Antimicrob Agents Chemother"
                        "fecha" => "2007"
                        "volumen" => "51"
                        "paginaInicial" => "2253"
                        "paginaFinal" => "2256"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Candida parapsilosis</span> is a significant neonatal pathogen&#58; a systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "Pediatr Infect Dis J"
                        "fecha" => "2013"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "67"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Adhesion of <span class="elsevierStyleItalic">Candida parapsilosis</span> to epithelial and acrylic surfaces correlates with cell surface hydrophobicity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Mycoses"
                        "fecha" => "2001"
                        "volumen" => "44"
                        "paginaInicial" => "29"
                        "paginaFinal" => "35"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biofilm formation by <span class="elsevierStyleItalic">Candida albican</span>s mutants for genes coding fungal proteins exhibiting the eight-cysteine-containing CFEM domain"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1567-1364.2006.00131.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "FEMS Yeast Res"
                        "fecha" => "2006"
                        "volumen" => "6"
                        "paginaInicial" => "1074"
                        "paginaFinal" => "1084"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology of invasive candidiasis&#58; a persistent public health problem"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/CMR.00029-06"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Microbiol Rev"
                        "fecha" => "2007"
                        "volumen" => "20"
                        "paginaInicial" => "133"
                        "paginaFinal" => "163"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "International surveillance of bloodstream infections due to <span class="elsevierStyleItalic">Candida</span> species&#58; frequency of occurrence and antifungal susceptibilities of isolates collected in 1997 in the United States&#44; Canada&#44; and South America for the SENTRY Program&#46; The SENTRY Participant Group"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Microbiol"
                        "fecha" => "1998"
                        "volumen" => "36"
                        "paginaInicial" => "1886"
                        "paginaFinal" => "1889"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Candida parapsilosis</span> infection following the electrosurgery procedure"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1529-8019.2010.01386.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dermatol Ther"
                        "fecha" => "2011"
                        "volumen" => "24"
                        "paginaInicial" => "131"
                        "paginaFinal" => "133"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            71 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "72"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Synthesis and turnover of non-polar lipids in yeast"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.plipres.2008.01.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Prog Lipid Res"
                        "fecha" => "2008"
                        "volumen" => "47"
                        "paginaInicial" => "157"
                        "paginaFinal" => "171"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            72 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "73"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The filamentation pathway controlled by the Efg1 regulator protein is required for normal biofilm formation and development in <span class="elsevierStyleItalic">Candida albicans</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "FEMS Microbiol Lett"
                        "fecha" => "2002"
                        "volumen" => "214"
                        "paginaInicial" => "95"
                        "paginaFinal" => "100"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            73 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "74"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Multicenter study of fungemia due to yeasts in Argentina"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Argent Microbiol"
                        "fecha" => "2005"
                        "volumen" => "37"
                        "paginaInicial" => "189"
                        "paginaFinal" => "195"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            74 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "75"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Correlation between biofilm formation and the hypoxic response in <span class="elsevierStyleItalic">Candida parapsilosis</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/EC.00350-08"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eukaryot Cell"
                        "fecha" => "2009"
                        "volumen" => "8"
                        "paginaInicial" => "550"
                        "paginaFinal" => "559"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            75 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "76"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Transcriptional response of <span class="elsevierStyleItalic">Candida parapsilosis</span> following exposure to farnesol"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/AAC.01438.06"
                      "Revista" => array:6 [
                        "tituloSerie" => "Antimicrob Agents Chemother"
                        "fecha" => "2007"
                        "volumen" => "51"
                        "paginaInicial" => "2304"
                        "paginaFinal" => "2312"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            76 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "77"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Candida</span> acid proteinases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Med Vet Mycol"
                        "fecha" => "1992"
                        "volumen" => "30"
                        "numero" => "Suppl&#46; 1"
                        "paginaInicial" => "123"
                        "paginaFinal" => "132"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            77 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "78"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neonatal <span class="elsevierStyleItalic">Candida parapsilosis</span> outbreak with a high case fatality rate"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Infect Dis J"
                        "fecha" => "1995"
                        "volumen" => "14"
                        "paginaInicial" => "776"
                        "paginaFinal" => "781"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            78 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "79"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Transcriptional response of <span class="elsevierStyleItalic">Candida albicans</span> to hypoxia&#58; linkage of oxygen sensing and Efg1p-regulatory networks"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jmb.2006.06.040"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Mol Biol"
                        "fecha" => "2006"
                        "volumen" => "361"
                        "paginaInicial" => "399"
                        "paginaFinal" => "411"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            79 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "80"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Synthesis of triacylglycerols by the acyl-coenzyme A&#58; diacyl-glycerol acyltransferase Dga1p in lipid particles of the yeast <span class="elsevierStyleItalic">Saccharomyces cerevisiae</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Bacteriol"
                        "fecha" => "2002"
                        "volumen" => "184"
                        "paginaInicial" => "519"
                        "paginaFinal" => "524"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            80 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "81"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Candida parapsilosis</span>&#44; an emerging fungal pathogen"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/CMR.00013-08"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Microbiol Rev"
                        "fecha" => "2008"
                        "volumen" => "21"
                        "paginaInicial" => "606"
                        "paginaFinal" => "625"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            81 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "82"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biofilm production by <span class="elsevierStyleItalic">Candida</span> species and inadequate antifungal therapy as predictors of mortality for patients with candidemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/JCM.00131-07"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Microbiol"
                        "fecha" => "2007"
                        "volumen" => "45"
                        "paginaInicial" => "1843"
                        "paginaFinal" => "1850"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            82 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "83"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Candida parapsilosis</span>&#58; a review of its epidemiology&#44; pathogenesis&#44; clinical aspects&#44; typing and antimicrobial susceptibility"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/10408410903213393"
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Rev Microbiol"
                        "fecha" => "2009"
                        "volumen" => "35"
                        "paginaInicial" => "283"
                        "paginaFinal" => "309"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            83 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "84"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Molecular mechanisms of necroptosis&#58; an ordered cellular explosion"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrm2970"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Mol Cell Biol"
                        "fecha" => "2010"
                        "volumen" => "11"
                        "paginaInicial" => "700"
                        "paginaFinal" => "714"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            84 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "85"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Candida parapsilosis</span>&#58; epidemiology&#44; pathogenicity&#44; clinical manifestations&#44; and antimicrobial susceptibility"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Infect Dis"
                        "fecha" => "1992"
                        "volumen" => "14"
                        "paginaInicial" => "756"
                        "paginaFinal" => "766"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            85 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "86"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Candida parapsilosis</span> fungemia associated with parenteral nutrition and contaminated blood pressure transducers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Microbiol"
                        "fecha" => "1987"
                        "volumen" => "25"
                        "paginaInicial" => "1029"
                        "paginaFinal" => "1032"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            86 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "87"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nosocomial bloodstream infections in US hospitals&#58; analysis of 24&#44;179 cases from a prospective nationwide surveillance study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1086/421946"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Infect Dis"
                        "fecha" => "2004"
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Article information

ISSN: 11301406
Original language: English

DOI:10.1016/j.riam.2013.09.018

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2024 October	24	5	29
2024 September	66	18	84
2024 August	45	17	62
2024 July	42	22	64
2024 June	58	18	76
2024 May	49	25	74
2024 April	65	20	85
2024 March	92	21	113
2024 February	80	11	91
2024 January	61	31	92
2023 December	93	48	141
2023 November	82	48	130
2023 October	95	48	143
2023 September	57	36	93
2023 August	46	15	61
2023 July	86	12	98
2023 June	101	16	117
2023 May	134	9	143
2023 April	115	5	120
2023 March	106	14	120
2023 February	81	15	96
2023 January	75	14	89
2022 December	68	23	91
2022 November	68	18	86
2022 October	40	20	60
2022 September	45	15	60
2022 August	37	16	53
2022 July	43	18	61
2022 June	43	12	55
2022 May	64	25	89
2022 April	66	24	90
2022 March	122	28	150
2022 February	100	15	115
2022 January	162	24	186
2021 December	69	25	94
2021 November	74	14	88
2021 October	86	40	126
2021 September	77	24	101
2021 August	91	16	107
2021 July	47	19	66
2021 June	53	21	74
2021 May	47	17	64
2021 April	123	48	171
2021 March	64	32	96
2021 February	19	20	39
2021 January	30	27	57
2020 December	27	17	44
2020 November	41	16	57
2020 October	23	12	35
2020 September	37	19	56
2020 August	32	21	53
2020 July	17	10	27
2020 June	21	10	31
2020 May	32	10	42
2020 April	35	6	41
2020 March	24	8	32
2020 February	31	4	35
2020 January	24	4	28
2019 December	23	9	32
2019 November	19	15	34
2019 October	35	4	39
2019 September	26	4	30
2019 August	15	18	33
2019 July	19	19	38
2019 June	49	21	70
2019 May	113	45	158
2019 April	62	40	102
2019 March	13	7	20
2019 February	20	6	26
2019 January	10	7	17
2018 December	19	9	28
2018 November	32	9	41
2018 October	23	19	42
2018 September	34	4	38
2018 August	24	4	28
2018 July	17	6	23
2018 June	28	6	34
2018 May	22	9	31
2018 April	27	2	29
2018 March	11	1	12
2018 February	14	1	15
2018 January	18	3	21
2017 December	10	2	12
2017 November	18	2	20
2017 October	24	1	25
2017 September	12	7	19
2017 August	14	5	19
2017 July	16	2	18
2017 June	78	12	90
2017 May	25	6	31
2017 April	30	2	32
2017 March	27	44	71
2017 February	25	1	26
2017 January	29	3	32
2016 December	34	7	41
2016 November	40	7	47
2016 October	53	7	60
2016 September	53	7	60
2016 August	33	1	34
2016 July	28	4	32
2016 June	59	21	80
2016 May	34	12	46
2016 April	20	6	26
2016 March	30	10	40
2016 February	22	10	32
2016 January	27	14	41
2015 December	26	8	34
2015 November	63	7	70
2015 October	25	6	31
2015 September	28	8	36
2015 August	50	8	58
2015 July	54	8	62
2015 June	29	8	37
2015 May	64	9	73
2015 April	156	20	176
2015 March	18	10	28
2015 February	20	4	24
2015 January	14	10	24
2014 December	14	3	17
2014 November	16	3	19
2014 October	13	4	17
2014 September	23	12	35
2014 August	33	11	44
2014 July	23	11	34
2014 June	19	9	28
2014 May	14	12	26
2014 April	19	13	32
2014 March	24	14	38
2014 February	16	4	20

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