Identification of Mucor circinelloides antigens recognized by sera from immunocompromised infected mice

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Javier Cabañes" "autores" => array:1 [ 0 => array:2 [ "nombre" => "F. Javier" "apellidos" => "Cabañes" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1130140620300188?idApp=UINPBA00004N" "url" => "/11301406/0000003700000034/v2_202012290734/S1130140620300188/v2_202012290734/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Identification of Mucor circinelloides antigens recognized by sera from immunocompromised infected mice" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "81" "paginaFinal" => "86" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Maialen Areitio, Adela Martin-Vicente, Aitana Arbizu, Aitziber Antoran, Leire Aparicio-Fernandez, Idoia Buldain, Leire Martin-Souto, Aitor Rementeria, Javier Capilla, Fernando L. Hernando, Andoni Ramirez-Garcia" "autores" => array:11 [ 0 => array:3 [ "nombre" => "Maialen" "apellidos" => "Areitio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Adela" "apellidos" => "Martin-Vicente" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "Aitana" "apellidos" => "Arbizu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Aitziber" "apellidos" => "Antoran" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Leire" "apellidos" => "Aparicio-Fernandez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Idoia" "apellidos" => "Buldain" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Leire" "apellidos" => "Martin-Souto" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 7 => array:3 [ "nombre" => "Aitor" "apellidos" => "Rementeria" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 8 => array:3 [ "nombre" => "Javier" "apellidos" => "Capilla" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 9 => array:4 [ "nombre" => "Fernando L." "apellidos" => "Hernando" "email" => array:1 [ 0 => "fl.hernando@ehu.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 10 => array:3 [ "nombre" => "Andoni" "apellidos" => "Ramirez-Garcia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Fungal and Bacterial Biomics Research Group, Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Mycology Unit, Medical School and IISPV, Universitat Rovira i Virgili, Reus, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Clinical Pharmacy and Translational Science, University of Tennessee Health Science Center, Memphis, TN, USA" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Identificación de antígenos de Mucor circinelloides reconocidos por sueros de ratones inmunodeprimidos infectados" ] ] "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" => 1164 "Ancho" => 2500 "Tamanyo" => 318360 ] ] "descripcion" => array:1 [ "en" => "Analysis of 2-DE of the total extract of Mucor circinelloides. (a) Stained with Coomassie Brilliant Blue and (b) WB obtained with the sera of immunocompromised infected mice." ] ] ] "textoCompleto" => "Mucor circinelloides is a saprophyte and pathogenic fungus which affects, above all, immunocompromised individuals, both human and animal. According to a recent review of cases of mucormycosis between January 2000 and January 2017, Mucor species are the second most common causal agent of mucormycosis, only outnumbered by fungi within the genus Rhizopus.<a class="elsevierStyleCrossRef" href="#bib0170">9</a> In the last few years the incidence of mucormycosis has increased, the principal cause being the marked rise in debilitating diseases of the immune system, which includes pathologies such as bone marrow or solid organ transplantations, immunodeficiencies related to HIV, diabetes and primary or iatrogenic neutropenia.<a class="elsevierStyleCrossRef" href="#bib0175">10</a> Recently, it has also caused an outbreak in burned patients.<a class="elsevierStyleCrossRef" href="#bib0155">6</a> Mucormycosis can occur by inhalation of airborne conidia or inoculation on an open wound,<a class="elsevierStyleCrossRef" href="#bib0215">18</a> it is highly aggressive and spreads quickly, invading the blood vessels, causing hemorrhages, thrombosis, heart attacks and tissue necrosis. In addition, it must be taken into account the fact that diagnosis is usually carried out at a late stage of infection, and that treatment strategies are not clear.<a class="elsevierStyleCrossRefs" href="#bib0230">21,22</a> Because of these reasons outlined above and the fact that it is an emerging pathology, more research into this disease is of paramount importance.<a class="elsevierStyleCrossRef" href="#bib0160">7</a> Therefore, the aim of this work was to achieve the identification of the most immunogenic antigens of M. circinelloides. To do that, an innovative approach using immunosuppressed mice was employed to detect them so that only the most immunoreactive were selected.Materials and methodsStrains and culture conditionsThe strain of M. circinelloides used in this study was CBS 125721, isolated from human maxillary tissue. It was cryopreserved at −80°C and cultured onto Potato Dextrose Agar (PDA) (Pronadisa, Madrid, Spain) at 28°C for 7 days before use. The conidiospores were obtained by washing the plates with sterile saline (0.9% NaCl), filtered through gauze and centrifuged. The concentration of conidiospores was adjusted as needed using a hemocytometer.Animal modelsThe sera used for the detection of the most immunoreactive antigens were obtained from two groups of 5 mice each immunosupressed with cyclophosphamide: one was infected with fungal conidia, and the other one was injected with saline solution, according to a method previously described.<a class="elsevierStyleCrossRef" href="#bib0190">13</a> Briefly, the mice were immunosuppressed 2 days prior the infection by intraperitoneal injection of 200mg/kg body weight of cyclophosphamide and once every 5 days thereafter, and inoculated intravenously with a density of 105 conidia or saline solution and sacrificed 20 days later. All experiments involving animals were in accordance with the ethical standards of Universitat Rovira i Virgili Animal Welfare and Ethics Comittee.Obtention of total protein extract and secretome of M. circinelloidesFor the total extract and the secretome, 5×105conidia/ml and 106conidia/ml were grown, respectively, for 24h at 37°C and 120rpm in 150ml Potato Dextrose Broth (PDB). After culture, both conidia and hyphae morphologies were obtained. Then, the fungus was centrifuged (12,000×g, 5min, 4°C), and washed with PBS.For the total extract the pellet was resuspended in PBS with 1% β-mercaptoethanol and 1% pharmalytes, then it was lysed using crystal beads (0.5mm diameter) at 30Hz for 20min using the Millmix 20 Bead-Beater (Thetnica, Eslovenia, Europe).The secretome was obtained as described by da Silva et al.<a class="elsevierStyleCrossRef" href="#bib0150">5</a> for Scedosporiumboydii, with a few modifications. After growing in PDB, the fungus was collected and cultured in PBS-2% glucose for 20h at 37°C and 120rpm. Finally, the obtained culture was centrifuged at 11,000×g for 20min and the supernatant was sterilized through 0.22μm filters (Merck Millipore, MAS, USA). To confirm the absence of cytoplasmic proteins in the secretome the activity of the intracellular enzyme lactate dehydrogenase (LDH) was measured, as previously described,<a class="elsevierStyleCrossRef" href="#bib0240">23</a> and the cellular integrity of the fungus was observed under optical microscopy.Protein detection by two-dimensional electrophoresisThe proteins were precipitated and two-dimensional electrophoresis (2-DE) was carried out following the protocol described in a previous work,<a class="elsevierStyleCrossRef" href="#bib0200">15</a> using 18cm long Immobiline DryStrip gels (pH 3–10, GE Healthcare). The conditions of the isoelectric focusing were modified for the secretome: 12h rehydration, 150V for 300Vhr (Step and Hold, S&H), 500V for 2000Vhr (S&H), 1000V for 9000Vhr (gradient), 8000V for 20,000Vhr (gradient) and 8000V for 100,000Vhr (S&H). The second dimension was carried out in the PROTEAN II xi Cell system (Bio-Rad, CA, USA) at 45mA using 10% polyacrylamide gels. The 2-DE gels were stained with Coomassie Brilliant Blue to visualize proteins.Antigen detectionProteins were electrotransferred to Hybond-P PVDF membranes, which were stained with Ponceau red to check the correct transfer of the proteins. Then, Western Blot (WB) was performed in accordance with the protocol described by Pellon et al.<a class="elsevierStyleCrossRef" href="#bib0200">15</a> using the sera of infected mice, pooled and diluted 1/100 as sample. The experiments were carried out in triplicate and the most immunoreactive antigens were selected using ImageMaster 2D Platinum software (GE Healthcare).Identification of immunoreactive proteinsThe identified spots were extracted from the gels for identification by mass spectrometry (LC–MS/MS) in the service of proteomics SGIker of the University of the Basque Country (UPV/EHU), as described by Buldain et al.<a class="elsevierStyleCrossRef" href="#bib0135">2</a> Briefly, the extracted gel pieces were swollen in digestion buffer (50mM NH4HCO3, 12.5ng/μl trypsin [Roche, Basel, Switzerland]) and incubated at 37°C overnight. After that, the peptides were extracted, first with 25mM NH4HCO3 and acetonitrile (ACN), and secondly with 0.1% (v/v) trifluoroacetic acid and ACN. LC–MS/MS was carried out on a SYNAPT HDMS mass spectrometer (Waters, Milford, MA, USA) interfaced with a nanoAcquity UPLC System (Waters). The search for protein identification was made in the non-redundant database of the NCBI, restricted to fungi, using the online server MASCOT (Matrix Science Ltd., London, UK (<a href="http://www.matrixscience.com/">http://www.matrixscience.com</a>).Bioinformatic analysis of M. circinelloides antigensIn order to study the relation between the identified antigens and their homologues in other organisms, the BLAST database (<a href="https://blast.ncbi.nlm.nih.gov/Blast.cgi">https://blast.ncbi.nlm.nih.gov/Blast.cgi</a>) was used. Then, the similarity values found between the proteins were compared.ResultsInoculation of immunosuppressed mice with M. circinelloidesIn this study, mice immunosuppressed with cyclophosphamide were used to reduce the immune response and, in consequence, to avoid excessive immunoreactivity in WBs. Besides, we selected a strain of M. circinelloides previously classified as avirulent, which allowed us to collect the sera from all mice as the mortality rate in both infected and non-infected groups was zero. All the data of the infection process using this avirulent strain were described in a previous study.<a class="elsevierStyleCrossRef" href="#bib0190">13</a>Identification of the immunoreactive antigens of the secretome recognized by sera of immunocompromised infected miceThe proteomics study of the secretome of M. circinelloides by 2-DE showed that secreted proteins were localized throughout the whole isoelectric point (pI) range used and with molecular weights (Mr) smaller than 130kDa. Specifically, the majority of the proteins contained in the secretome presented a pI between 4.5 and 7, and a Mr between 25 and 70kDa (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Sera of immunocompromised infected mice were used against the obtained extract; the immunoreactivity was analyzed and the seven most immunoreactive antigens were identified by mass spectrometry (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Three of these spots corresponded to enolase and four to triosephosphate isomerase, as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. They are almost certainly isoforms of the enolase and triosephosphate isomerase, respectively, as they have the same molecular weights and very similar isoelectric points, as it can be observed in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a. The sera of mice injected with saline solution were also used at the same dilution and, as expected, no reactivity was observed (data not shown).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Identification of the immunoreactive antigens of the total extract recognized by sera of immunocompromised infected miceRegarding the study of the fungal cell proteome of the total extract by 2-DE, the proteins detected were also localized on the whole range of pI and Mr used. However, the protein distribution pattern observed was very different from the secretome and almost all proteins were present in the ranges of pI of 5–9 and Mr of 40–70kDa (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>a).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>The immunome detected by two-dimensional WB showed a very few number of immunoreactive proteins recognized by sera from immunosuppressed mice and, therefore, only the two most immunoreactive spots were selected for their further identification (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). These proteins were identified by mass spectrometry as enolase and heat shock protein HSS1 (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). In the same way than for the secretome, the sera of mice injected with saline solution did not show any immunoreactivity (data not shown).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Bioinformatic analysis of the identified proteinsWhen comparing the sequence of the identified triosephosphate isomerase with the genome of M. circinelloides, an identity value of 99.48% was found. The Hsp70 identified in our work has similarity values of 78.58%, 76.43% and 66.39% with the proteins SSA1 and SSA2 found in Candida albicans, and the Hsp70 found in Rhizopus arrhizus, respectively. Finally, the sequence of the enolase of M. circinelloides was compared with the enolase of C. albicans, R. arrhizus and Homo sapiens, and similarity values of 69%, 81.88% and 71% were found, respectively.DiscussionDue to the increase of immune system debilitating diseases in the last years, the prevalence of many infections has arisen. Mucormycosis is one of these infectious diseases, which can be caused by the fungus M. circinelloides. Mucormycosis is known for its high aggressiveness and quick spreading. Besides, due to the late diagnosis in the majority of the cases and the presence of high percentage of resistant isolates, this disease has high mortality rates.Therefore, the aim of this work was to identify the most immunoreactive antigens of M. circinelloides, analyzing the immune response produced by sera obtained from immunocompromised infected mice. We used a cyclophosphamide-based immunosuppressive treatment to reduce the humoral immune response and, therefore, avoid the excess of signal which might mask and difficult the interpretation of the results. In this way, we proceeded to the identification of only the most immunogenic antigens by LC–MS/MS.As a result, we identified in the secretome extract, from seven immunoreactive spots, two proteins, being them enolase and triosephosphate isomerase; in the total extract, from two spots, two proteins were identified, enolase and heat-shock protein HSS1. Among the proteins identified in the secretome extract, three isoforms of enolase and four of triosephosphate isomerase were detected. The spectrometric identifications showed that the proteins are probably the product of the same gene and, therefore, the little differences found among the pI values of these proteins might be due to slight modifications during the secretion process.As enolase and triosephosphate isomerase, usually cytoplasmic proteins, were detected in the secretome, the mechanism of their secretion and function are not completely understood. The secretion process involved in M. circinelloides could be through extracellular vesicles, as seen with triosephosphate isomerase of the dimorphic fungus Paracoccidioides brasiliensis.<a class="elsevierStyleCrossRef" href="#bib0185">12</a> Besides, taking into account the plasminogen binding activities of these two proteins, their presence in the external medium could be related to pathogen dissemination.<a class="elsevierStyleCrossRef" href="#bib0145">4</a>Although triosephosphate isomerase was detected in the secretome extract of M. circinelloides, the identification by LC–MS/MS of the selected spot resulted in the fungus of the same genus Mucor ambiguus, because the used database determined this protein as the one found in this microorganism. When comparing this protein sequence with the genome of M. circinelloides, an identity value of 99.48% was found, indicating the high degree of similarity between the sequences of triosephosphate isomerase in both species. This protein was also identified in the fungi C. albicans<a class="elsevierStyleCrossRef" href="#bib0220">19</a> and P. brasiliensis, and it is considered an important antigen, capable of binding the laminin and fibronectin of the extracellular matrix.<a class="elsevierStyleCrossRef" href="#bib0210">17</a> Moreover, it can be found in the cell wall, but also in the secreted extracellular vesicles.<a class="elsevierStyleCrossRef" href="#bib0185">12</a>Regarding HSS1, it belongs to the same heat shock protein family as the Hsp70,<a class="elsevierStyleCrossRef" href="#bib0130">1</a> which in fungal species is overexpressed during infection to prevent the denaturalization of proteins<a class="elsevierStyleCrossRef" href="#bib0195">14</a> and has been described as immunoreactive against serum IgGs<a class="elsevierStyleCrossRef" href="#bib0200">15</a> and mucosal IgAs.<a class="elsevierStyleCrossRef" href="#bib0205">16</a> In fact, HSS1 could be considered an orthologue of the Hsp70 proteins, SSA1 and SSA2, found in the ascomycetous fungi C. albicans, and the Hsp70 of R. arrhizus, as it shares with those proteins similarity values higher than 65%. Although there is a high percentage of homology, there are some specific regions when compared with the sequences of SSA1 of C. albicans and Hsp70 of R. arrhizus. This fact could be of great interest for diagnosis. Heat-shock proteins have been reported as antigens and virulence factors in the cell surface<a class="elsevierStyleCrossRef" href="#bib0200">15</a> and the secretome of important pathogenic fungi, such as Lomentospora prolificans.<a class="elsevierStyleCrossRef" href="#bib0140">3</a> In this sense, the location of the protein could ease the access of the immune cells, contributing to the high immunogenicity presented. Besides, it has been proved that the Hsp70 of Mycobacterium tuberculosis is capable of inducing the immune response, stimulating human monocytes to produce chemokines and cytokines.<a class="elsevierStyleCrossRef" href="#bib0245">24</a> Given the major functions that Hsp70 has on infective processes and the homology between this protein and the one found in our study, it could be hypothesized that the protein HSS1 could have a similar role in the infections caused by M. circinelloides.Enolase deserves a special mention as it has been identified in both analyzed protein extracts. Enolase has been also identified in the secretome of the mycelia and yeast cells of the dimorphic fungus Paracoccidioides lutzii.<a class="elsevierStyleCrossRef" href="#bib0250">25</a> This metabolic enzyme was also previously identified by our research group as an antigen recognized by salivary IgA in L. prolificans,<a class="elsevierStyleCrossRef" href="#bib0135">2</a> and by serum IgGs in C. albicans.<a class="elsevierStyleCrossRef" href="#bib0165">8</a> Enolase was also associated with the cell wall in L. prolificans<a class="elsevierStyleCrossRef" href="#bib0200">15</a> and C. albicans,<a class="elsevierStyleCrossRef" href="#bib0195">14</a> where it performs transglutaminase activity, indicating the possible role of this enzyme in infection processes.<a class="elsevierStyleCrossRef" href="#bib0225">20</a> Enolase, therefore, seems to be an important antigen for many of the most common pathogenic fungi, which makes it a reasonable target in panfungal diagnosis or a key to design new treatments or vaccines. In fact, the use of this enzyme for therapy was tested as a vaccine against C. albicans, lowering both the fungal burden and the amount of tissue damage.<a class="elsevierStyleCrossRef" href="#bib0180">11</a>In order to determine the possible use of this protein in diagnosis or treatment strategies, its sequence was compared with the sequence in C. albicans, R. arrhizus and H. sapiens, and the similarity values found make probable a cross-reactivity with other fungi, as it happens between enolase of L. prolificans and Scedosporium apiospermum, S. boydii and Aspergillus fumigatus.<a class="elsevierStyleCrossRef" href="#bib0195">14</a> Hence, although it could not be used for a specific diagnosis or therapeutic target, it could be used as a panfungal antigen.In conclusion, in this work the most immunoreactive antigens of the secretome and the total extract of M. circinelloides were identified. The proteins identified were the HSS1 protein, along with enolase and triosephosphate isomerase, which are well-known fungal antigens. These proteins might be useful in the future for the development of a vaccine, antifungal treatments and/or for diagnosis, allowing the rapid detection and treatment of the disease and, therefore, lowering the unacceptable mortality rates.FundingThis study was funded by the University of the Basque Country (UPV/EHU) [grant number PPG17/41] and by the Basque Government [grant number IT1362-19]. MA and LMS have received a Grant from the Basque Government and LAF from the UPV/EHU.Authors contributionsAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by MA, LMS and ARG. The first draft of the manuscript was written by MA and all authors commented on previous versions of the manuscript. All authors read and approved the final version.Conflict of interestThe authors declare that they have no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1442124" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Aims" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1316161" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1442123" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1316160" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Materials and methods" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Strains and culture conditions" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Animal models" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Obtention of total protein extract and secretome of M. circinelloides" ] 3 => array:2 [ "identificador" => "sec0025" "titulo" => "Protein detection by two-dimensional electrophoresis" ] 4 => array:2 [ "identificador" => "sec0030" "titulo" => "Antigen detection" ] 5 => array:2 [ "identificador" => "sec0035" "titulo" => "Identification of immunoreactive proteins" ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Bioinformatic analysis of M. circinelloides antigens" ] ] ] 5 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Inoculation of immunosuppressed mice with M. circinelloides" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Identification of the immunoreactive antigens of the secretome recognized by sera of immunocompromised infected mice" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Identification of the immunoreactive antigens of the total extract recognized by sera of immunocompromised infected mice" ] 3 => array:2 [ "identificador" => "sec0065" "titulo" => "Bioinformatic analysis of the identified proteins" ] ] ] 6 => array:2 [ "identificador" => "sec0070" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0075" "titulo" => "Funding" ] 8 => array:2 [ "identificador" => "sec0080" "titulo" => "Authors contributions" ] 9 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interest" ] 10 => array:2 [ "identificador" => "xack503365" "titulo" => "Acknowledgments" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-03-12" "fechaAceptado" => "2020-07-07" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1316161" "palabras" => array:6 [ 0 => "Diagnostic target" 1 => "Antigen" 2 => "Mucormycosis" 3 => "Immunoreactive protein" 4 => "Serological antigen" 5 => "Antigen detection" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1316160" "palabras" => array:6 [ 0 => "Diana diagnóstica" 1 => "Antígeno" 2 => "Mucormicosis" 3 => "Proteína inmunorreactiva" 4 => "Antígeno serológico" 5 => "Detección antigénica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundMucor circinelloides is an opportunistic fungus capable of causing mucormycosis, a highly aggressive infection of quick spreading. Besides, it also has a high mortality rate due to late diagnosis and difficult treatment. AimsIn this study we have identified the most immunoreactive proteins of the secretome and the total protein extract of M. circinelloides using sera from immunocompromised infected mice. MethodsThe proteins of the secretome and the total extract were analyzed by two-dimensional electrophoresis and the most immunoreactive antigens were detected by Western Blot, facing the sera of immunocompromised infected mice to the proteins obtained in both extracts of M. circinelloides. ResultsSeven antigens were detected in the secretome extract, and two in the total extract, all of them corresponding only to three proteins. The enzyme enolase was detected in both extracts, while triosephosphate isomerase was detected in the secretome, and heat shock protein HSS1 in the total extract. ConclusionsIn this work the most immunoreactive antigens of the secretome and the total extract of M. circinelloides were identified. The identified proteins are well known fungal antigens and, therefore, these findings can be useful for future research into alternatives for the diagnosis and treatment of mucormycosis." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Aims" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "AntecedentesMucor circinelloides es un hongo oportunista causante de la mucormicosis, una infección altamente agresiva y de rápida expansión. Además, también presenta una alta mortalidad debido al diagnóstico tardío y el difícil tratamiento. ObjetivosEn este estudio se han identificado las proteínas más inmunorreactivas del secretoma y del extracto total de proteínas de M. circinelloides mediante el uso de sueros obtenidos de ratones inmunodeprimidos infectados. MétodosLas proteínas del secretoma y del extracto total se analizaron mediante electroforesis bidimensional y se detectaron los antígenos más inmunorreactivos mediante Western Blot, enfrentando el suero de los ratones inmunodeprimidos infectados a las proteínas obtenidas en ambos extractos de M. circinelloides. ResultadosSe identificaron 7 antígenos en el secretoma y 2 en el extracto total, todos ellos correspondientes a 3 proteínas. La enolasa se detectó en ambos extractos, mientras que la triosafosfato isomerasa se detectó en el secretoma, y la proteína de choque térmico HSS1 en el extracto total. ConclusionesEn este trabajo se identificaron los antígenos más inmunorreactivos del secretoma y del extracto total de M. circinelloides. Todas las proteínas identificadas son antígenos fúngicos muy conocidos y, por ello, estos resultados pueden ser de gran utilidad en futuras investigaciones relacionadas con la mejora del diagnóstico y el tratamiento de la mucormicosis." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1168 "Ancho" => 2500 "Tamanyo" => 303132 ] ] "descripcion" => array:1 [ "en" => "Analysis of 2-DE of the secretome of Mucor circinelloides. (a) Stained with Coomassie Brilliant Blue and (b) WB obtained with the sera of immunocompromised infected mice." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1164 "Ancho" => 2500 "Tamanyo" => 318360 ] ] "descripcion" => array:1 [ "en" => "Analysis of 2-DE of the total extract of Mucor circinelloides. (a) Stained with Coomassie Brilliant Blue and (b) WB obtained with the sera of immunocompromised infected mice." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Spot number \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NCBI number \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Name of the protein \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Microorganism \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Matches \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cover (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Score \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Theoretical pI/Mr (kDa) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Experimental pI/Mr (kDa) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EPB85979.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Enolase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mucor circinelloides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">855 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.56/47.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.44/54.14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EPB85979.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Enolase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mucor circinelloides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1093 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.56/47.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.65/54.66 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EPB85979.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Enolase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mucor circinelloides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">317 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.56/47.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.76/54.66 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GAN00908.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Triosephosphate isomerase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mucor ambiguus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">319 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.26/26.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.23/26.28 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GAN00908.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Triosephosphate isomerase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mucor ambiguus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">537 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.26/26.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.00/26.57 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GAN00908.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Triosephosphate isomerase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mucor ambiguus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">807 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.26/26.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.24/26.79 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GAN00908.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Triosephosphate isomerase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mucor ambiguus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">663 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.26/26.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.50/26.79 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2480408.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Analysis of the antigens identified in the secretome of Mucor circinelloides. Different parameters of the identifications are shown." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Spot number \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NCBI number \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Name of the protein \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Microorganism \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Matches \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cover (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Score \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Theoretical pI/Mr (kDa) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Experimental pI/Mr (kDa) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EPB85979.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Enolase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mucor circinelloides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1346 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.56/47.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.79/50.88 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EPB91082.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Heat-shock protein HSS1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mucor circinelloides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1530 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.07/70.92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.79/46.23 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2480407.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Analysis of the antigens identified in the total extract of Mucor circinelloides. Different parameters of the identifications are shown." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:25 [ 0 => array:3 [ "identificador" => "bib0130" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fungal transcript pattern during the preinfection stage (12h) of ectomycorrhiza formed between Pisolithustinctorius and Castaneasativa roots, identified using cDNA microarrays" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Acioli-Santos" 1 => "M. Sebastiana" 2 => "F. Pessoa" 3 => "L. Sousa" 4 => "A. Figueiredo" 5 => "A.M. Fortes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00284-008-9253-2" "Revista" => array:6 [ "tituloSerie" => "Curr Microbiol" "fecha" => "2008" "volumen" => "57" "paginaInicial" => "620" "paginaFinal" => "625" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18836771" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0135" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cyclophilin and enolase are the most prevalent conidial antigens of Lomentosporaprolificans recognized by healthy human salivary IgA and cross-react with Aspergillusfumigatus" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I. Buldain" 1 => "A. Ramirez-Garcia" 2 => "A. Pellon" 3 => "A. Antoran" 4 => "M.J. Sevilla" 5 => "A. Rementeria" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/prca.201600080" "Revista" => array:6 [ "tituloSerie" => "PROTEOMICS – Clin Appl" "fecha" => "2016" "volumen" => "10" "paginaInicial" => "1058" "paginaFinal" => "1067" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27485921" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0140" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Study of humoral responses against Lomentospora/Scedosporium spp. and Aspergillus fumigatus to identify L. prolificans antigens of interest for diagnosis and treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I. Buldain" 1 => "A. Pellon" 2 => "B. Zaldibar" 3 => "A. Antoran" 4 => "L. Martin-Souto" 5 => "L. Aparicio-Fernandez" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Vaccines (Basel)" "fecha" => "2019" "volumen" => "7" "paginaInicial" => "212" "paginaFinal" => "234" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0145" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of Paracoccidioides secreted proteins reveals fructose 1,6-bisphosphate aldolase as a plasminogen-binding protein" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.G. Chaves" 1 => "S.S. Weber" 2 => "S.N. Báo" 3 => "L.A. Pereira" 4 => "A.M. Bailão" 5 => "C.L. Borges" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12866-015-0393-9" "Revista" => array:6 [ "tituloSerie" => "BMC Microbiol" "fecha" => "2015" "volumen" => "15" "paginaInicial" => "53" "paginaFinal" => "67" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25888027" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0150" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Proteomic analysis of the secretions of Pseudallescheriaboydii, a human fungal pathogen with unknown genome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B.A. Da Silva" 1 => "C.L. Sodré" 2 => "A.L. Souza-Gonçalves" 3 => "A.C. Aor" 4 => "L.F. Kneipp" 5 => "B.B. Fonseca" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1021/pr200875x" "Revista" => array:6 [ "tituloSerie" => "J Proteome Res" "fecha" => "2012" "volumen" => "11" "paginaInicial" => "172" "paginaFinal" => "188" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22142336" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0155" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outbreak of invasive wound mucormycosis in a burn unit due to multiple trains of Mucor circinelloides f. circinelloides resolved by whole-genome sequencing" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Garcia-Hermoso" 1 => "A. Criscuolo" 2 => "S.C. Lee" 3 => "M. Legrand" 4 => "M. Chaouat" 5 => "B. Denis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/mBio.00673-18" "Revista" => array:6 [ "tituloSerie" => "MBio" "fecha" => "2018" "volumen" => "9" "paginaInicial" => "e00673" "paginaFinal" => "e718" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29991586" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0160" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mucormycosis caused by unusual mucormycetes, non-Rhizopus, -Mucor, and -Lichtheimia species" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.Z.R. Gomes" 1 => "R.E. Lewis" 2 => "D.P. Kontoyiannis" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Microbiol Rev" "fecha" => "2011" "volumen" => "24" "paginaInicial" => "411" "paginaFinal" => "445" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0165" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification of protein and mannoprotein antigens of Candidaalbicans of relevance for the serodiagnosis of invasive candidiasis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.L. Hernando" 1 => "E. Calvo" 2 => "A. Abad" 3 => "A. Ramirez" 4 => "A. Rementeria" 5 => "M.J. Sevilla" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Int Microbiol" "fecha" => "2007" "volumen" => "10" "paginaInicial" => "103" "paginaFinal" => "108" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17661288" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0170" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chen SC-A. The epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "W. Jeong" 1 => "C. Keighley" 2 => "R. Wolfe" 3 => "W.L. Lee" 4 => "M.A. Slavin" 5 => "D.C.M. Kong" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cmi.2018.07.011" "Revista" => array:6 [ "tituloSerie" => "Clin Microbiol Infect" "fecha" => "2019" "volumen" => "25" "paginaInicial" => "26" "paginaFinal" => "34" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30036666" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0175" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of a food-borne fungal pathogen outbreak: virulence and genome of a Mucor circinelloides isolate from yogurt" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.C. Lee" 1 => "R.B. Billmyre" 2 => "A. Li" 3 => "S. Carson" 4 => "S.M. Sykes" 5 => "E.Y. Huh" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "MBio" "fecha" => "2014" "volumen" => "5" "paginaInicial" => "1" "paginaFinal" => "12" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0180" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunisation with the glycolytic enzyme enolase confers effective protection against Candidaalbicans infection in mice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W.Q. Li" 1 => "X.C. Hu" 2 => "X. Zhang" 3 => "Y. Ge" 4 => "S. Zhao" 5 => "Y. Hu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.vaccine.2011.05.030" "Revista" => array:6 [ "tituloSerie" => "Vaccine" "fecha" => "2011" "volumen" => "29" "paginaInicial" => "5526" "paginaFinal" => "5533" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21645574" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0185" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Proteome of cell wall-extracts from pathogenic Paracoccidioidesbrasiliensis: Comparison among morphological phases, isolates, and reported fungal extracellular vesicle proteins" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "L.V.G. Longo" 1 => "J.P.C. da Cunha" 2 => "T.J.P. Sobreira" 3 => "R. Puccia" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "EuPA Open Proteomics" "fecha" => "2014" "volumen" => "3" "paginaInicial" => "216" "paginaFinal" => "228" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0190" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Understanding Mucorcircinelloides pathogenesis by comparative genomics and phenotypical studies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Lopez-Fernandez" 1 => "M. Sanchis" 2 => "P. Navarro-Rodríguez" 3 => "F.E. Nicolás" 4 => "F. Silva-Franco" 5 => "J. Guarro" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/21505594.2018.1435249" "Revista" => array:6 [ "tituloSerie" => "Virulence" "fecha" => "2018" "volumen" => "9" "paginaInicial" => "707" "paginaFinal" => "720" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29436903" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0195" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hsp70 in parasites: as an inducible protective protein and as an antigen" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. Maresca" 1 => "G.S. Kobayashi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/BF01923463" "Revista" => array:6 [ "tituloSerie" => "Experientia" "fecha" => "1994" "volumen" => "50" "paginaInicial" => "1067" "paginaFinal" => "1074" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7988666" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0200" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunoproteomics-based analysis of the immunocompetent serological response to Lomentospora prolificans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Pellon" 1 => "A. Ramirez-Garcia" 2 => "I. Buldain" 3 => "A. Antoran" 4 => "A. Rementeria" 5 => "F.L. Hernando" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1021/acs.jproteome.5b00978" "Revista" => array:6 [ "tituloSerie" => "J Proteome Res" "fecha" => "2016" "volumen" => "15" "paginaInicial" => "595" "paginaFinal" => "607" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26732945" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0205" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Scedosporiumprolificans immunomes against human salivary immunoglobulin A" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Pellon" 1 => "A. Ramirez-Garcia" 2 => "A. Antoran" 3 => "J.V. Fernandez-Molina" 4 => "A. Abad-Diaz-De-Cerio" 5 => "D. Montañez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.funbio.2013.11.006" "Revista" => array:6 [ "tituloSerie" => "Fungal Biol" "fecha" => "2014" "volumen" => "118" "paginaInicial" => "94" "paginaFinal" => "105" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24433680" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0210" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of the Paracoccidioidesbrasiliensis triosephosphate isomerase suggests the potential for adhesin function" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.A. Pereira" 1 => "S.N. Báo" 2 => "M.S. Barbosa" 3 => "J.L.M. da Silva" 4 => "M.S.S. Felipe" 5 => "J.M. de Santana" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1567-1364.2007.00292.x" "Revista" => array:6 [ "tituloSerie" => "FEMS Yeast Res" "fecha" => "2007" "volumen" => "7" "paginaInicial" => "1381" "paginaFinal" => "1388" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17714474" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0215" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology and clinical manifestations of mucormycosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G. Petrikkos" 1 => "A. Skiada" 2 => "O. Lortholary" 3 => "E. Roilides" 4 => "T.J. Walsh" 5 => "D.P. Kontoyiannis" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2012" "volumen" => "54" "numero" => "Suppl. 1" "paginaInicial" => "23" "paginaFinal" => "34" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0220" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of the serologic response to systemic Candida albicans infection in a murine model" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Pitarch" 1 => "R. Díez-Orejas" 2 => "G. Molero" 3 => "M. Pardo" 4 => "M. Sánchez" 5 => "C. Gil" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/1615-9861(200104)1:4<550::AID-PROT550>3.0.CO;2-W" "Revista" => array:6 [ "tituloSerie" => "Proteomics" "fecha" => "2001" "volumen" => "1" "paginaInicial" => "550" "paginaFinal" => "559" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11681208" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0225" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Candida albicans ENO1 gene encodes a transglutaminase involved in growth, cell division, morphogenesis and osmotic protection" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Reyna-Beltran" 1 => "M. Iranzo" 2 => "K.G. Calderón-González" 3 => "R. Mondragón-Flores" 4 => "M.L. Labra-Barrios" 5 => "S. Mormeneo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1074/jbc.M117.810440" "Revista" => array:6 [ "tituloSerie" => "J Biol Chem" "fecha" => "2018" "volumen" => "293" "paginaInicial" => "4304" "paginaFinal" => "4323" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29386353" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0230" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology and outcome of zygomycosis: a review of 929 reported cases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.M. Roden" 1 => "T.E. Zaoutis" 2 => "W.L. Buchanan" 3 => "T.A. Knudsen" 4 => "T.A. Sarkisova" 5 => "R.L. Schaufele" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/432579" "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2005" "volumen" => "41" "paginaInicial" => "634" "paginaFinal" => "653" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16080086" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0235" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular identification of zygomycetes from culture and experimentally infected tissues" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Schwarz" 1 => "S. Bretagne" 2 => "J.C. Gantier" 3 => "D. García-Hermoso" 4 => "O. Lortholary" 5 => "F. Dromer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/JCM.44.2.340-349.2006" "Revista" => array:6 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "2006" "volumen" => "44" "paginaInicial" => "340" "paginaFinal" => "349" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16455881" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0240" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pseudallescheria boydii releases metallopeptidases capable of cleaving several proteinaceous compounds" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "B.A. Silva" 1 => "M.R. Pinto" 2 => "R.M.A. Soares" 3 => "E. Barreto-Bergter" 4 => "A.L.S. Santos" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.resmic.2005.11.010" "Revista" => array:6 [ "tituloSerie" => "Res Microbiol" "fecha" => "2006" "volumen" => "157" "paginaInicial" => "425" "paginaFinal" => "432" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16487686" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0245" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Stimulation of Th1-polarizing cytokines. C–C chemokines, maturation of dendritic cells, and adjuvant function by the peptide binding fragment of heat shock protein 70" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Wang" 1 => "C.G. Kelly" 2 => "M. Singh" 3 => "E.G. McGowan" 4 => "A.S. Carrara" 5 => "L.A. Bergmeier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4049/jimmunol.169.5.2422" "Revista" => array:6 [ "tituloSerie" => "J Immunol" "fecha" => "2002" "volumen" => "169" "paginaInicial" => "2422" "paginaFinal" => "2429" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12193710" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0250" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of the secretomes of Paracoccidioides mycelia and yeast cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S.S. Weber" 1 => "A.F. Parente" 2 => "C.L. Borges" 3 => "J.A. Parente" 4 => "A.M. Bailão" 5 => "C.M. de Almeida Soares" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0052470" "Revista" => array:5 [ "tituloSerie" => "PLoS One" "fecha" => "2012" "volumen" => "7" "paginaInicial" => "e52470" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23272246" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack503365" "titulo" => "Acknowledgments" "texto" => "We thank the member of the Chartered of Linguists, No. 022913 for improving the English in the manuscript." 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Identification of Mucor circinelloides antigens recognized by sera from immunocompromised infected mice

Identificación de antígenos de Mucor circinelloides reconocidos por sueros de ratones inmunodeprimidos infectados

Maialen Areitioa, Adela Martin-Vicenteb,c, Aitana Arbizua, Aitziber Antorana, Leire Aparicio-Fernandeza, Idoia Buldaina, Leire Martin-Soutoa, Aitor Rementeriaa, Javier Capillab, Fernando L. Hernandoa,

Corresponding author

fl.hernando@ehu.es

Corresponding author.

, Andoni Ramirez-Garciaa

a Fungal and Bacterial Biomics Research Group, Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Spain

b Mycology Unit, Medical School and IISPV, Universitat Rovira i Virgili, Reus, Spain

c Department of Clinical Pharmacy and Translational Science, University of Tennessee Health Science Center, Memphis, TN, USA

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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Mucor circinelloides</span> is a saprophyte and pathogenic fungus which affects&#44; above all&#44; immunocompromised individuals&#44; both human and animal&#46; According to a recent review of cases of mucormycosis between January 2000 and January 2017&#44; <span class="elsevierStyleItalic">Mucor</span> species are the second most common causal agent of mucormycosis&#44; only outnumbered by fungi within the genus <span class="elsevierStyleItalic">Rhizopus</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">9</span></a> In the last few years the incidence of mucormycosis has increased&#44; the principal cause being the marked rise in debilitating diseases of the immune system&#44; which includes pathologies such as bone marrow or solid organ transplantations&#44; immunodeficiencies related to HIV&#44; diabetes and primary or iatrogenic neutropenia&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">10</span></a> Recently&#44; it has also caused an outbreak in burned patients&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a> Mucormycosis can occur by inhalation of airborne conidia or inoculation on an open wound&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">18</span></a> it is highly aggressive and spreads quickly&#44; invading the blood vessels&#44; causing hemorrhages&#44; thrombosis&#44; heart attacks and tissue necrosis&#46; In addition&#44; it must be taken into account the fact that diagnosis is usually carried out at a late stage of infection&#44; and that treatment strategies are not clear&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">21&#44;22</span></a> Because of these reasons outlined above and the fact that it is an emerging pathology&#44; more research into this disease is of paramount importance&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">7</span></a> Therefore&#44; the aim of this work was to achieve the identification of the most immunogenic antigens of <span class="elsevierStyleItalic">M&#46; circinelloides</span>&#46; To do that&#44; an innovative approach using immunosuppressed mice was employed to detect them so that only the most immunoreactive were selected&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Materials and methods</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Strains and culture conditions</span><p id="par0010" class="elsevierStylePara elsevierViewall">The strain of <span class="elsevierStyleItalic">M&#46; circinelloides</span> used in this study was CBS 125721&#44; isolated from human maxillary tissue&#46; It was cryopreserved at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C and cultured onto Potato Dextrose Agar &#40;PDA&#41; &#40;Pronadisa&#44; Madrid&#44; Spain&#41; at 28<span class="elsevierStyleHsp" style=""></span>&#176;C for 7 days before use&#46; The conidiospores were obtained by washing the plates with sterile saline &#40;0&#46;9&#37; NaCl&#41;&#44; filtered through gauze and centrifuged&#46; The concentration of conidiospores was adjusted as needed using a hemocytometer&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Animal models</span><p id="par0015" class="elsevierStylePara elsevierViewall">The sera used for the detection of the most immunoreactive antigens were obtained from two groups of 5 mice each immunosupressed with cyclophosphamide&#58; one was infected with fungal conidia&#44; and the other one was injected with saline solution&#44; according to a method previously described&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">13</span></a> Briefly&#44; the mice were immunosuppressed 2 days prior the infection by intraperitoneal injection of 200<span class="elsevierStyleHsp" style=""></span>mg&#47;kg body weight of cyclophosphamide and once every 5 days thereafter&#44; and inoculated intravenously with a density of 10<span class="elsevierStyleSup">5</span> conidia or saline solution and sacrificed 20 days later&#46; All experiments involving animals were in accordance with the ethical standards of Universitat Rovira i Virgili Animal Welfare and Ethics Comittee&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Obtention of total protein extract and secretome of <span class="elsevierStyleItalic">M&#46; circinelloides</span></span><p id="par0020" class="elsevierStylePara elsevierViewall">For the total extract and the secretome&#44; 5<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">5</span><span class="elsevierStyleHsp" style=""></span>conidia&#47;ml and 10<span class="elsevierStyleSup">6</span><span class="elsevierStyleHsp" style=""></span>conidia&#47;ml were grown&#44; respectively&#44; for 24<span class="elsevierStyleHsp" style=""></span>h at 37<span class="elsevierStyleHsp" style=""></span>&#176;C and 120<span class="elsevierStyleHsp" style=""></span>rpm in 150<span class="elsevierStyleHsp" style=""></span>ml Potato Dextrose Broth &#40;PDB&#41;&#46; After culture&#44; both conidia and hyphae morphologies were obtained&#46; Then&#44; the fungus was centrifuged &#40;12&#44;000<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">g</span>&#44; 5<span class="elsevierStyleHsp" style=""></span>min&#44; 4<span class="elsevierStyleHsp" style=""></span>&#176;C&#41;&#44; and washed with PBS&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">For the total extract the pellet was resuspended in PBS with 1&#37; &#946;-mercaptoethanol and 1&#37; pharmalytes&#44; then it was lysed using crystal beads &#40;0&#46;5<span class="elsevierStyleHsp" style=""></span>mm diameter&#41; 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MAS&#44; USA&#41;&#46; To confirm the absence of cytoplasmic proteins in the secretome the activity of the intracellular enzyme lactate dehydrogenase &#40;LDH&#41; was measured&#44; as previously described&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">23</span></a> and the cellular integrity of the fungus was observed under optical microscopy&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Protein detection by two-dimensional electrophoresis</span><p id="par0035" class="elsevierStylePara elsevierViewall">The proteins were precipitated and two-dimensional electrophoresis &#40;2-DE&#41; was carried out following the protocol described in a previous work&#44;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">15</span></a> using 18<span class="elsevierStyleHsp" style=""></span>cm long Immobiline DryStrip gels &#40;pH 3&#8211;10&#44; GE Healthcare&#41;&#46; 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polyacrylamide gels&#46; The 2-DE gels were stained with Coomassie Brilliant Blue to visualize proteins&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Antigen detection</span><p id="par0040" class="elsevierStylePara elsevierViewall">Proteins were electrotransferred to Hybond-P PVDF membranes&#44; which were stained with Ponceau red to check the correct transfer of the proteins&#46; Then&#44; Western Blot &#40;WB&#41; was performed in accordance with the protocol described by Pellon et al&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">15</span></a> using the sera of infected mice&#44; pooled and diluted 1&#47;100 as sample&#46; The experiments were carried out in triplicate and the most immunoreactive antigens were selected using ImageMaster 2D Platinum software &#40;GE Healthcare&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Identification of immunoreactive proteins</span><p id="par0045" class="elsevierStylePara elsevierViewall">The identified spots were extracted from the gels for identification by mass spectrometry &#40;LC&#8211;MS&#47;MS&#41; in the service of proteomics SGIker of the University of the Basque Country &#40;UPV&#47;EHU&#41;&#44; as described by Buldain et al&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> Briefly&#44; the extracted gel pieces were swollen in digestion buffer &#40;50<span class="elsevierStyleHsp" style=""></span>mM NH<span class="elsevierStyleInf">4</span>HCO<span class="elsevierStyleInf">3</span>&#44; 12&#46;5<span class="elsevierStyleHsp" style=""></span>ng&#47;&#956;l trypsin &#91;Roche&#44; Basel&#44; Switzerland&#93;&#41; and incubated at 37<span class="elsevierStyleHsp" style=""></span>&#176;C overnight&#46; After that&#44; the peptides were extracted&#44; first with 25<span class="elsevierStyleHsp" style=""></span>mM NH<span class="elsevierStyleInf">4</span>HCO<span class="elsevierStyleInf">3</span> and acetonitrile &#40;ACN&#41;&#44; and secondly with 0&#46;1&#37; &#40;v&#47;v&#41; trifluoroacetic acid and ACN&#46; LC&#8211;MS&#47;MS was carried out on a SYNAPT HDMS mass spectrometer &#40;Waters&#44; Milford&#44; MA&#44; USA&#41; interfaced with a nanoAcquity UPLC System &#40;Waters&#41;&#46; The search for protein identification was made in the non-redundant database of the NCBI&#44; restricted to fungi&#44; using the online server MASCOT &#40;Matrix Science Ltd&#46;&#44; London&#44; UK &#40;<a href="http://www.matrixscience.com/">http&#58;&#47;&#47;www&#46;matrixscience&#46;com</a>&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Bioinformatic analysis of <span class="elsevierStyleItalic">M&#46; circinelloides</span> antigens</span><p id="par0050" class="elsevierStylePara elsevierViewall">In order to study the relation between the identified antigens and their homologues in other organisms&#44; the BLAST database &#40;<a href="https://blast.ncbi.nlm.nih.gov/Blast.cgi">https&#58;&#47;&#47;blast&#46;ncbi&#46;nlm&#46;nih&#46;gov&#47;Blast&#46;cgi</a>&#41; was used&#46; Then&#44; the similarity values found between the proteins were compared&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Inoculation of immunosuppressed mice with <span class="elsevierStyleItalic">M&#46; circinelloides</span></span><p id="par0055" class="elsevierStylePara elsevierViewall">In this study&#44; mice immunosuppressed with cyclophosphamide were used to reduce the immune response and&#44; in consequence&#44; to avoid excessive immunoreactivity in WBs&#46; Besides&#44; we selected a strain of <span class="elsevierStyleItalic">M&#46; circinelloides</span> previously classified as avirulent&#44; which allowed us to collect the sera from all mice as the mortality rate in both infected and non-infected groups was zero&#46; All the data of the infection process using this avirulent strain were described in a previous study&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">13</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Identification of the immunoreactive antigens of the secretome recognized by sera of immunocompromised infected mice</span><p id="par0060" class="elsevierStylePara elsevierViewall">The proteomics study of the secretome of <span class="elsevierStyleItalic">M&#46; circinelloides</span> by 2-DE showed that secreted proteins were localized throughout the whole isoelectric point &#40;p<span class="elsevierStyleItalic">I&#41;</span> range used and with molecular weights &#40;Mr&#41; smaller than 130<span class="elsevierStyleHsp" style=""></span>kDa&#46; Specifically&#44; the majority of the proteins contained in the secretome presented a p<span class="elsevierStyleItalic">I</span> between 4&#46;5 and 7&#44; and a Mr between 25 and 70<span class="elsevierStyleHsp" style=""></span>kDa &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>a&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Sera of immunocompromised infected mice were used against the obtained extract&#59; the immunoreactivity was analyzed and the seven most immunoreactive antigens were identified by mass spectrometry &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Three of these spots corresponded to enolase and four to triosephosphate isomerase&#44; as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; They are almost certainly isoforms of the enolase and triosephosphate isomerase&#44; respectively&#44; as they have the same molecular weights and very similar isoelectric points&#44; as it can be observed in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>a&#46; The sera of mice injected with saline solution were also used at the same dilution and&#44; as expected&#44; no reactivity was observed &#40;data not shown&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Identification of the immunoreactive antigens of the total extract recognized by sera of immunocompromised infected mice</span><p id="par0070" class="elsevierStylePara elsevierViewall">Regarding the study of the fungal cell proteome of the total extract by 2-DE&#44; the proteins detected were also localized on the whole range of p<span class="elsevierStyleItalic">I</span> and Mr used&#46; However&#44; the protein distribution pattern observed was very different from the secretome and almost all proteins were present in the ranges of p<span class="elsevierStyleItalic">I</span> of 5&#8211;9 and Mr of 40&#8211;70<span class="elsevierStyleHsp" style=""></span>kDa &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>a&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">The immunome detected by two-dimensional WB showed a very few number of immunoreactive proteins recognized by sera from immunosuppressed mice and&#44; therefore&#44; only the two most immunoreactive spots were selected for their further identification &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; These proteins were identified by mass spectrometry as enolase and heat shock protein HSS1 &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; In the same way than for the secretome&#44; the sera of mice injected with saline solution did not show any immunoreactivity &#40;data not shown&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Bioinformatic analysis of the identified proteins</span><p id="par0080" class="elsevierStylePara elsevierViewall">When comparing the sequence of the identified triosephosphate isomerase with the genome of <span class="elsevierStyleItalic">M&#46; circinelloides</span>&#44; an identity value of 99&#46;48&#37; was found&#46; The Hsp70 identified in our work has similarity values of 78&#46;58&#37;&#44; 76&#46;43&#37; and 66&#46;39&#37; with the proteins SSA1 and SSA2 found in <span class="elsevierStyleItalic">Candida albicans&#44;</span> and the Hsp70 found in <span class="elsevierStyleItalic">Rhizopus arrhizus</span>&#44; respectively<span class="elsevierStyleItalic">&#46;</span> Finally&#44; the sequence of the enolase of <span class="elsevierStyleItalic">M&#46; circinelloides</span> was compared with the enolase of <span class="elsevierStyleItalic">C&#46; albicans</span>&#44; <span class="elsevierStyleItalic">R&#46; arrhizus</span> and <span class="elsevierStyleItalic">Homo sapiens</span>&#44; and similarity values of 69&#37;&#44; 81&#46;88&#37; and 71&#37; were found&#44; respectively&#46;</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">Due to the increase of immune system debilitating diseases in the last years&#44; the prevalence of many infections has arisen&#46; Mucormycosis is one of these infectious diseases&#44; which can be caused by the fungus <span class="elsevierStyleItalic">M&#46; circinelloides</span>&#46; Mucormycosis is known for its high aggressiveness and quick spreading&#46; Besides&#44; due to the late diagnosis in the majority of the cases and the presence of high percentage of resistant isolates&#44; this disease has high mortality rates&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Therefore&#44; the aim of this work was to identify the most immunoreactive antigens of <span class="elsevierStyleItalic">M&#46; circinelloides</span>&#44; analyzing the immune response produced by sera obtained from immunocompromised infected mice&#46; We used a cyclophosphamide-based immunosuppressive treatment to reduce the humoral immune response and&#44; therefore&#44; avoid the excess of signal which might mask and difficult the interpretation of the results&#46; In this way&#44; we proceeded to the identification of only the most immunogenic antigens by LC&#8211;MS&#47;MS&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">As a result&#44; we identified in the secretome extract&#44; from seven immunoreactive spots&#44; two proteins&#44; being them enolase and triosephosphate isomerase&#59; in the total extract&#44; from two spots&#44; two proteins were identified&#44; enolase and heat-shock protein HSS1&#46; Among the proteins identified in the secretome extract&#44; three isoforms of enolase and four of triosephosphate isomerase were detected&#46; The spectrometric identifications showed that the proteins are probably the product of the same gene and&#44; therefore&#44; the little differences found among the p<span class="elsevierStyleItalic">I</span> values of these proteins might be due to slight modifications during the secretion process&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">As enolase and triosephosphate isomerase&#44; usually cytoplasmic proteins&#44; were detected in the secretome&#44; the mechanism of their secretion and function are not completely understood&#46; The secretion process involved in <span class="elsevierStyleItalic">M&#46; circinelloides</span> could be through extracellular vesicles&#44; as seen with triosephosphate isomerase of the dimorphic fungus <span class="elsevierStyleItalic">Paracoccidioides brasiliensis</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a> Besides&#44; taking into account the plasminogen binding activities of these two proteins&#44; their presence in the external medium could be related to pathogen dissemination&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">4</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Although triosephosphate isomerase was detected in the secretome extract of <span class="elsevierStyleItalic">M&#46; circinelloides</span>&#44; the identification by LC&#8211;MS&#47;MS of the selected spot resulted in the fungus of the same genus <span class="elsevierStyleItalic">Mucor ambiguus</span>&#44; because the used database determined this protein as the one found in this microorganism&#46; When comparing this protein sequence with the genome of <span class="elsevierStyleItalic">M&#46; circinelloides</span>&#44; an identity value of 99&#46;48&#37; was found&#44; indicating the high degree of similarity between the sequences of triosephosphate isomerase in both species&#46; This protein was also identified in the fungi <span class="elsevierStyleItalic">C&#46; albicans</span><a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">19</span></a> and <span class="elsevierStyleItalic">P&#46; brasiliensis</span>&#44; and it is considered an important antigen&#44; capable of binding the laminin and fibronectin of the extracellular matrix&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">17</span></a> Moreover&#44; it can be found in the cell wall&#44; but also in the secreted extracellular vesicles&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Regarding HSS1&#44; it belongs to the same heat shock protein family as the Hsp70&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">1</span></a> which in fungal species is overexpressed during infection to prevent the denaturalization of proteins<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">14</span></a> and has been described as immunoreactive against serum IgGs<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">15</span></a> and mucosal IgAs&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">16</span></a> In fact&#44; HSS1 could be considered an orthologue of the Hsp70 proteins&#44; SSA1 and SSA2&#44; found in the ascomycetous fungi <span class="elsevierStyleItalic">C&#46; albicans</span>&#44; and the Hsp70 of <span class="elsevierStyleItalic">R&#46; arrhizus</span>&#44; as it shares with those proteins similarity values higher than 65&#37;&#46; Although there is a high percentage of homology&#44; there are some specific regions when compared with the sequences of SSA1 of <span class="elsevierStyleItalic">C&#46; albicans</span> and Hsp70 of <span class="elsevierStyleItalic">R&#46; arrhizus</span>&#46; This fact could be of great interest for diagnosis&#46; Heat-shock proteins have been reported as antigens and virulence factors in the cell surface<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">15</span></a> and the secretome of important pathogenic fungi&#44; such as <span class="elsevierStyleItalic">Lomentospora prolificans</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">3</span></a> In this sense&#44; the location of the protein could ease the access of the immune cells&#44; contributing to the high immunogenicity presented&#46; Besides&#44; it has been proved that the Hsp70 of <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> is capable of inducing the immune response&#44; stimulating human monocytes to produce chemokines and cytokines&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">24</span></a> Given the major functions that Hsp70 has on infective processes and the homology between this protein and the one found in our study&#44; it could be hypothesized that the protein HSS1 could have a similar role in the infections caused by <span class="elsevierStyleItalic">M&#46; circinelloides</span>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Enolase deserves a special mention as it has been identified in both analyzed protein extracts&#46; Enolase has been also identified in the secretome of the mycelia and yeast cells of the dimorphic fungus <span class="elsevierStyleItalic">Paracoccidioides lutzii</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">25</span></a> This metabolic enzyme was also previously identified by our research group as an antigen recognized by salivary IgA in <span class="elsevierStyleItalic">L&#46; prolificans</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> and by serum IgGs in <span class="elsevierStyleItalic">C&#46; albicans</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">8</span></a> Enolase was also associated with the cell wall in <span class="elsevierStyleItalic">L&#46; prolificans</span><a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">15</span></a> and <span class="elsevierStyleItalic">C&#46; albicans</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">14</span></a> where it performs transglutaminase activity&#44; indicating the possible role of this enzyme in infection processes&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">20</span></a> Enolase&#44; therefore&#44; seems to be an important antigen for many of the most common pathogenic fungi&#44; which makes it a reasonable target in panfungal diagnosis or a key to design new treatments or vaccines&#46; In fact&#44; the use of this enzyme for therapy was tested as a vaccine against <span class="elsevierStyleItalic">C&#46; albicans</span>&#44; lowering both the fungal burden and the amount of tissue damage&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">11</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">In order to determine the possible use of this protein in diagnosis or treatment strategies&#44; its sequence was compared with the sequence in <span class="elsevierStyleItalic">C&#46; albicans</span>&#44; <span class="elsevierStyleItalic">R&#46; arrhizus</span> and <span class="elsevierStyleItalic">H&#46; sapiens</span>&#44; and the similarity values found make probable a cross-reactivity with other fungi&#44; as it happens between enolase of <span class="elsevierStyleItalic">L&#46; prolificans</span> and <span class="elsevierStyleItalic">Scedosporium apiospermum</span>&#44; <span class="elsevierStyleItalic">S&#46; boydii</span> and <span class="elsevierStyleItalic">Aspergillus fumigatus</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">14</span></a> Hence&#44; although it could not be used for a specific diagnosis or therapeutic target&#44; it could be used as a panfungal antigen&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In conclusion&#44; in this work the most immunoreactive antigens of the secretome and the total extract of <span class="elsevierStyleItalic">M&#46; circinelloides</span> were identified&#46; The proteins identified were the HSS1 protein&#44; along with enolase and triosephosphate isomerase&#44; which are well-known fungal antigens&#46; These proteins might be useful in the future for the development of a vaccine&#44; antifungal treatments and&#47;or for diagnosis&#44; allowing the rapid detection and treatment of the disease and&#44; therefore&#44; lowering the unacceptable mortality rates&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Funding</span><p id="par0130" class="elsevierStylePara elsevierViewall">This study was funded by the <span class="elsevierStyleGrantSponsor" id="gs1">University of the Basque Country &#40;UPV&#47;EHU&#41;</span> &#91;grant number <span class="elsevierStyleGrantNumber" refid="gs1">PPG17&#47;41</span>&#93; and by the <span class="elsevierStyleGrantSponsor" id="gs2">Basque Government</span> &#91;grant number <span class="elsevierStyleGrantNumber" refid="gs2">IT1362-19</span>&#93;&#46; MA and LMS have received a Grant from the Basque Government and LAF from the UPV&#47;EHU&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Authors contributions</span><p id="par0135" class="elsevierStylePara elsevierViewall">All authors contributed to the study conception and design&#46; Material preparation&#44; data collection and analysis were performed by MA&#44; LMS and ARG&#46; The first draft of the manuscript was written by MA and all authors commented on previous versions of the manuscript&#46; All authors read and approved the final version&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Conflict of interest</span><p id="par0140" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Mucor circinelloides</span> is an opportunistic fungus capable of causing mucormycosis&#44; a highly aggressive infection of quick spreading&#46; Besides&#44; it also has a high mortality rate due to late diagnosis and difficult treatment&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Aims</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">In this study we have identified the most immunoreactive proteins of the secretome and the total protein extract of <span class="elsevierStyleItalic">M&#46; circinelloides</span> using sera from immunocompromised infected mice&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The proteins of the secretome and the total extract were analyzed by two-dimensional electrophoresis and the most immunoreactive antigens were detected by Western Blot&#44; facing the sera of immunocompromised infected mice to the proteins obtained in both extracts of <span class="elsevierStyleItalic">M&#46; circinelloides</span>&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Seven antigens were detected in the secretome extract&#44; and two in the total extract&#44; all of them corresponding only to three proteins&#46; The enzyme enolase was detected in both extracts&#44; while triosephosphate isomerase was detected in the secretome&#44; and heat shock protein HSS1 in the total extract&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">In this work the most immunoreactive antigens of the secretome and the total extract of <span class="elsevierStyleItalic">M&#46; circinelloides</span> were identified&#46; The identified proteins are well known fungal antigens and&#44; therefore&#44; these findings can be useful for future research into alternatives for the diagnosis and treatment of mucormycosis&#46;</p></span>"
        "secciones" => array:5 [
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            "identificador" => "abst0005"
            "titulo" => "Background"
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            "titulo" => "Aims"
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            "titulo" => "Conclusions"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antecedentes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Mucor circinelloides</span> es un hongo oportunista causante de la mucormicosis&#44; una infecci&#243;n altamente agresiva y de r&#225;pida expansi&#243;n&#46; Adem&#225;s&#44; tambi&#233;n presenta una alta mortalidad debido al diagn&#243;stico tard&#237;o y el dif&#237;cil tratamiento&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">En este estudio se han identificado las prote&#237;nas m&#225;s inmunorreactivas del secretoma y del extracto total de prote&#237;nas de <span class="elsevierStyleItalic">M&#46; circinelloides</span> mediante el uso de sueros obtenidos de ratones inmunodeprimidos infectados&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Las prote&#237;nas del secretoma y del extracto total se analizaron mediante electroforesis bidimensional y se detectaron los ant&#237;genos m&#225;s inmunorreactivos mediante Western Blot&#44; enfrentando el suero de los ratones inmunodeprimidos infectados a las prote&#237;nas obtenidas en ambos extractos de <span class="elsevierStyleItalic">M&#46; circinelloides</span>&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se identificaron 7 ant&#237;genos en el secretoma y 2 en el extracto total&#44; todos ellos correspondientes a 3 prote&#237;nas&#46; La enolasa se detect&#243; en ambos extractos&#44; mientras que la triosafosfato isomerasa se detect&#243; en el secretoma&#44; y la prote&#237;na de choque t&#233;rmico HSS1 en el extracto total&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">En este trabajo se identificaron los ant&#237;genos m&#225;s inmunorreactivos del secretoma y del extracto total de <span class="elsevierStyleItalic">M&#46; circinelloides&#46;</span> Todas las prote&#237;nas identificadas son ant&#237;genos f&#250;ngicos muy conocidos y&#44; por ello&#44; estos resultados pueden ser de gran utilidad en futuras investigaciones relacionadas con la mejora del diagn&#243;stico y el tratamiento de la mucormicosis&#46;</p></span>"
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                  \t\t\t\t">Triosephosphate isomerase&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Triosephosphate isomerase&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5&#46;26&#47;26&#46;95&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Triosephosphate isomerase&nbsp;\t\t\t\t\t\t\n
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                  """
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Spot number&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Enolase&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Mucor circinelloides</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">46&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Heat-shock protein HSS1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Mucor circinelloides</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1530&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;07&#47;70&#46;92&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5&#46;79&#47;46&#46;23&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Analysis of the antigens identified in the total extract of <span class="elsevierStyleItalic">Mucor circinelloides</span>&#46; Different parameters of the identifications are shown&#46;</p>"
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      ]
    ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Fungal transcript pattern during the preinfection stage &#40;12<span class="elsevierStyleHsp" style=""></span>h&#41; of ectomycorrhiza formed between <span class="elsevierStyleItalic">Pisolithus</span><span class="elsevierStyleItalic">tinctorius</span> and <span class="elsevierStyleItalic">Castanea</span><span class="elsevierStyleItalic">sativa</span> roots&#44; identified using cDNA microarrays"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Acioli-Santos"
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                            2 => "F&#46; Pessoa"
                            3 => "L&#46; Sousa"
                            4 => "A&#46; Figueiredo"
                            5 => "A&#46;M&#46; Fortes"
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                    0 => array:2 [
                      "doi" => "10.1007/s00284-008-9253-2"
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                        "tituloSerie" => "Curr Microbiol"
                        "fecha" => "2008"
                        "volumen" => "57"
                        "paginaInicial" => "620"
                        "paginaFinal" => "625"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18836771"
                            "web" => "Medline"
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              "identificador" => "bib0135"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Cyclophilin and enolase are the most prevalent conidial antigens of <span class="elsevierStyleItalic">Lomentospora</span><span class="elsevierStyleItalic">prolificans</span> recognized by healthy human salivary IgA and cross-react with <span class="elsevierStyleItalic">Aspergillus</span><span class="elsevierStyleItalic">fumigatus</span>"
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                          "autores" => array:6 [
                            0 => "I&#46; Buldain"
                            1 => "A&#46; Ramirez-Garcia"
                            2 => "A&#46; Pellon"
                            3 => "A&#46; Antoran"
                            4 => "M&#46;J&#46; Sevilla"
                            5 => "A&#46; Rementeria"
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                        "tituloSerie" => "PROTEOMICS &#8211; Clin Appl"
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                        "paginaInicial" => "1058"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27485921"
                            "web" => "Medline"
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                      "titulo" => "Study of humoral responses against <span class="elsevierStyleItalic">Lomentospora&#47;Scedosporium</span> spp&#46; and <span class="elsevierStyleItalic">Aspergillus fumigatus</span> to identify <span class="elsevierStyleItalic">L&#46; prolificans</span> antigens of interest for diagnosis and treatment"
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                            2 => "B&#46; Zaldibar"
                            3 => "A&#46; Antoran"
                            4 => "L&#46; Martin-Souto"
                            5 => "L&#46; Aparicio-Fernandez"
                          ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Vaccines &#40;Basel&#41;"
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                        "volumen" => "7"
                        "paginaInicial" => "212"
                        "paginaFinal" => "234"
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                    ]
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              ]
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            3 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "4"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Analysis of <span class="elsevierStyleItalic">Paracoccidioides</span> secreted proteins reveals fructose 1&#44;6-bisphosphate aldolase as a plasminogen-binding protein"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;G&#46; Chaves"
                            1 => "S&#46;S&#46; Weber"
                            2 => "S&#46;N&#46; B&#225;o"
                            3 => "L&#46;A&#46; Pereira"
                            4 => "A&#46;M&#46; Bail&#227;o"
                            5 => "C&#46;L&#46; Borges"
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                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "BMC Microbiol"
                        "fecha" => "2015"
                        "volumen" => "15"
                        "paginaInicial" => "53"
                        "paginaFinal" => "67"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25888027"
                            "web" => "Medline"
                          ]
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                ]
              ]
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            4 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Proteomic analysis of the secretions of <span class="elsevierStyleItalic">Pseudallescheria</span><span class="elsevierStyleItalic">boydii</span>&#44; a human fungal pathogen with unknown genome"
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                            1 => "C&#46;L&#46; Sodr&#233;"
                            2 => "A&#46;L&#46; Souza-Gon&#231;alves"
                            3 => "A&#46;C&#46; Aor"
                            4 => "L&#46;F&#46; Kneipp"
                            5 => "B&#46;B&#46; Fonseca"
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                    0 => array:2 [
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                        "tituloSerie" => "J Proteome Res"
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                        "volumen" => "11"
                        "paginaInicial" => "172"
                        "paginaFinal" => "188"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22142336"
                            "web" => "Medline"
                          ]
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                ]
              ]
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              "identificador" => "bib0155"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outbreak of invasive wound mucormycosis in a burn unit due to multiple trains of <span class="elsevierStyleItalic">Mucor circinelloides f&#46; circinelloides</span> resolved by whole-genome sequencing"
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Garcia-Hermoso"
                            1 => "A&#46; Criscuolo"
                            2 => "S&#46;C&#46; Lee"
                            3 => "M&#46; Legrand"
                            4 => "M&#46; Chaouat"
                            5 => "B&#46; Denis"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/mBio.00673-18"
                      "Revista" => array:6 [
                        "tituloSerie" => "MBio"
                        "fecha" => "2018"
                        "volumen" => "9"
                        "paginaInicial" => "e00673"
                        "paginaFinal" => "e718"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29991586"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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            6 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "7"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mucormycosis caused by unusual mucormycetes&#44; non-<span class="elsevierStyleItalic">Rhizopus</span>&#44; -<span class="elsevierStyleItalic">Mucor</span>&#44; and -<span class="elsevierStyleItalic">Lichtheimia</span> species"
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                          "autores" => array:3 [
                            0 => "M&#46;Z&#46;R&#46; Gomes"
                            1 => "R&#46;E&#46; Lewis"
                            2 => "D&#46;P&#46; Kontoyiannis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Microbiol Rev"
                        "fecha" => "2011"
                        "volumen" => "24"
                        "paginaInicial" => "411"
                        "paginaFinal" => "445"
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0165"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Identification of protein and mannoprotein antigens of <span class="elsevierStyleItalic">Candida</span><span class="elsevierStyleItalic">albicans</span> of relevance for the serodiagnosis of invasive candidiasis"
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                            1 => "E&#46; Calvo"
                            2 => "A&#46; Abad"
                            3 => "A&#46; Ramirez"
                            4 => "A&#46; Rementeria"
                            5 => "M&#46;J&#46; Sevilla"
                          ]
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Int Microbiol"
                        "fecha" => "2007"
                        "volumen" => "10"
                        "paginaInicial" => "103"
                        "paginaFinal" => "108"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17661288"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0170"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Chen SC-A&#46; The epidemiology and clinical manifestations of mucormycosis&#58; a systematic review and meta-analysis of case reports"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
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                            1 => "C&#46; Keighley"
                            2 => "R&#46; Wolfe"
                            3 => "W&#46;L&#46; Lee"
                            4 => "M&#46;A&#46; Slavin"
                            5 => "D&#46;C&#46;M&#46; Kong"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cmi.2018.07.011"
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                        "tituloSerie" => "Clin Microbiol Infect"
                        "fecha" => "2019"
                        "volumen" => "25"
                        "paginaInicial" => "26"
                        "paginaFinal" => "34"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30036666"
                            "web" => "Medline"
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                0 => array:2 [
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                            3 => "S&#46; Carson"
                            4 => "S&#46;M&#46; Sykes"
                            5 => "E&#46;Y&#46; Huh"
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                    ]
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                        "paginaInicial" => "1"
                        "paginaFinal" => "12"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Immunisation with the glycolytic enzyme enolase confers effective protection against <span class="elsevierStyleItalic">Candida</span><span class="elsevierStyleItalic">albicans</span> infection in mice"
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                            3 => "Y&#46; Ge"
                            4 => "S&#46; Zhao"
                            5 => "Y&#46; Hu"
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                        "tituloSerie" => "Vaccine"
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                        "paginaInicial" => "5526"
                        "paginaFinal" => "5533"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21645574"
                            "web" => "Medline"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Proteome of cell wall-extracts from pathogenic <span class="elsevierStyleItalic">Paracoccidioides</span><span class="elsevierStyleItalic">brasiliensis</span>&#58; Comparison among morphological phases&#44; isolates&#44; and reported fungal extracellular vesicle proteins"
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                            3 => "R&#46; Puccia"
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                        "tituloSerie" => "EuPA Open Proteomics"
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                        "volumen" => "3"
                        "paginaInicial" => "216"
                        "paginaFinal" => "228"
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                    ]
                  ]
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            12 => array:3 [
              "identificador" => "bib0190"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Understanding <span class="elsevierStyleItalic">Mucor</span><span class="elsevierStyleItalic">circinelloides</span> pathogenesis by comparative genomics and phenotypical studies"
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                            3 => "F&#46;E&#46; Nicol&#225;s"
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                            5 => "J&#46; Guarro"
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                      ]
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                    0 => array:2 [
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                        "tituloSerie" => "Virulence"
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                        "volumen" => "9"
                        "paginaInicial" => "707"
                        "paginaFinal" => "720"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29436903"
                            "web" => "Medline"
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              "identificador" => "bib0195"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Hsp70 in parasites&#58; as an inducible protective protein and as an antigen"
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                          "etal" => false
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                        "tituloSerie" => "Experientia"
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                        "volumen" => "50"
                        "paginaInicial" => "1067"
                        "paginaFinal" => "1074"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7988666"
                            "web" => "Medline"
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              "identificador" => "bib0200"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunoproteomics-based analysis of the immunocompetent serological response to <span class="elsevierStyleItalic">Lomentospora prolificans</span>"
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                          "etal" => false
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                        "tituloSerie" => "J Proteome Res"
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                        "paginaInicial" => "595"
                        "paginaFinal" => "607"
                        "link" => array:1 [
                          0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Scedosporium</span><span class="elsevierStyleItalic">prolificans</span> immunomes against human salivary immunoglobulin A"
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                        "paginaFinal" => "105"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24433680"
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                ]
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              "identificador" => "bib0210"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Analysis of the <span class="elsevierStyleItalic">Paracoccidioides</span><span class="elsevierStyleItalic">brasiliensis</span> triosephosphate isomerase suggests the potential for adhesin function"
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                        "tituloSerie" => "FEMS Yeast Res"
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                        "paginaInicial" => "1381"
                        "paginaFinal" => "1388"
                        "link" => array:1 [
                          0 => array:2 [
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              "identificador" => "bib0215"
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                0 => array:2 [
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                      "titulo" => "Epidemiology and clinical manifestations of mucormycosis"
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                            5 => "D&#46;P&#46; Kontoyiannis"
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                  "host" => array:1 [
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Analysis of the serologic response to systemic <span class="elsevierStyleItalic">Candida albicans</span> infection in a murine model"
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                        "paginaFinal" => "559"
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              ]
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              "identificador" => "bib0225"
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                            4 => "M&#46;L&#46; Labra-Barrios"
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                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "2018"
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                      "titulo" => "Epidemiology and outcome of zygomycosis&#58; a review of 929 reported cases"
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                          "etal" => true
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                            3 => "T&#46;A&#46; Knudsen"
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                            5 => "R&#46;L&#46; Schaufele"
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                        "tituloSerie" => "Clin Infect Dis"
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                        "volumen" => "41"
                        "paginaInicial" => "634"
                        "paginaFinal" => "653"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16080086"
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                      ]
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                  ]
                ]
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                    0 => array:2 [
                      "titulo" => "Molecular identification of zygomycetes from culture and experimentally infected tissues"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Schwarz"
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                            2 => "J&#46;C&#46; Gantier"
                            3 => "D&#46; Garc&#237;a-Hermoso"
                            4 => "O&#46; Lortholary"
                            5 => "F&#46; Dromer"
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                        ]
                      ]
                    ]
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                    0 => array:2 [
                      "doi" => "10.1128/JCM.44.2.340-349.2006"
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                        "tituloSerie" => "J Clin Microbiol"
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                        "volumen" => "44"
                        "paginaInicial" => "340"
                        "paginaFinal" => "349"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16455881"
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                    ]
                  ]
                ]
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                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Pseudallescheria boydii</span> releases metallopeptidases capable of cleaving several proteinaceous compounds"
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                            4 => "A&#46;L&#46;S&#46; Santos"
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                        ]
                      ]
                    ]
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                    0 => array:2 [
                      "doi" => "10.1016/j.resmic.2005.11.010"
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                        "tituloSerie" => "Res Microbiol"
                        "fecha" => "2006"
                        "volumen" => "157"
                        "paginaInicial" => "425"
                        "paginaFinal" => "432"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16487686"
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                ]
              ]
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                    0 => array:2 [
                      "titulo" => "Stimulation of Th1-polarizing cytokines&#46; C&#8211;C chemokines&#44; maturation of dendritic cells&#44; and adjuvant function by the peptide binding fragment of heat shock protein 70"
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                        0 => array:2 [
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                            1 => "C&#46;G&#46; Kelly"
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                            4 => "A&#46;S&#46; Carrara"
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                        "paginaFinal" => "2429"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12193710"
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                        "paginaInicial" => "e52470"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23272246"
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Article information

ISSN: 11301406
Original language: English

DOI:10.1016/j.riam.2020.07.002

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Year/Month	Html	Pdf	Total

2024 November	24	3	27
2024 October	135	15	150
2024 September	111	23	134
2024 August	95	11	106
2024 July	87	13	100
2024 June	69	11	80
2024 May	98	13	111
2024 April	84	3	87
2024 March	145	6	151
2024 February	91	10	101
2024 January	93	7	100
2023 December	106	8	114
2023 November	114	7	121
2023 October	98	8	106
2023 September	53	7	60
2023 August	50	8	58
2023 July	52	3	55
2023 June	76	8	84
2023 May	118	7	125
2023 April	76	6	82
2023 March	93	24	117
2023 February	59	6	65
2023 January	43	12	55
2022 December	49	13	62
2022 November	49	18	67
2022 October	43	17	60
2022 September	36	19	55
2022 August	53	24	77
2022 July	40	34	74
2022 June	25	14	39
2022 May	36	12	48
2022 April	22	17	39
2022 March	53	39	92
2022 February	39	7	46
2022 January	49	12	61
2021 December	29	25	54
2021 November	52	11	63
2021 October	59	28	87
2021 September	31	13	44
2021 August	23	4	27
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2021 January	5	3	8
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