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Brief report
First detection of CMY-2 plasmid mediated β-lactamase in Salmonella Heidelberg in South America
Primera detección de CMY-2 en Salmonella Heidelberg en Sudamérica
Daniela Cejasa, Rafael Vignolib, Mirta Quinterosc, Ricardo Marinoc, Raquel Callejoc, Laura Betancorb, Gabriel O. Gutkinda, Marcela A. Radicea,
Corresponding author
mradice@ffyb.uba.ar

Corresponding author.
a Cátedra de Microbiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
b Departamento de Bacteriología y Virología, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
c Hospital de Infecciosas “F. Muñiz”, Ciudad Autónoma de Buenos Aires, Argentina
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Genetic context of <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span>&#46; ISE<span class="elsevierStyleItalic">cp1</span>&#58; Insertion sequence <span class="elsevierStyleItalic">Ecp1&#44; blc</span>&#58; gene encoding for outer membrane lipoprotein&#44;&#40;lipocalin&#41;&#59; <span class="elsevierStyleItalic">sugE</span>&#58; gene encoding for small multidrug resistance protein&#59; <span class="elsevierStyleItalic">ecnR</span>&#58; coding gene for a transcriptional regulatory protein&#44; entericidinR&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Salmonella enterica</span> serovar Heidelberg is the causative agent of salmonellosis&#44; a self-limiting gastroenteritis that does not usually require antibiotic therapy&#46; However&#44; severe infections may occur&#44; particularly in children and immunocompromised hosts&#44; leading to invasive diseases that require antimicrobial treatment&#46; Fluoroquinolones and extended-spectrum cephalosporins are frequently used in severe <span class="elsevierStyleItalic">Salmonella</span> infections<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Since the late &#8216;80s <span class="elsevierStyleItalic">Salmonella</span> isolates displaying resistance to extended spectrum cephalosporins have emerged worldwide&#46; Coding genes for TEM-&#44; SHV-&#44; PSE-&#44; OXA-&#44; PER-&#44; CTX-M-&#44; CMY-&#44; ACC-&#44; DHA- extended spectrum &#946;-lactamases &#40;ESBL&#41; and also KPC carbapenemases have been reported in <span class="elsevierStyleItalic">S&#46; enterica</span> isolates<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">S&#46; enterica</span> serovar Heidelberg ranks among the most prevalent causes of human salmonellosis in the United States and Canada&#44; although it is infrequently reported in South American and European countries<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; During the last decade&#44; extended-spectrum cephalosporin resistance has increased among human and agri-food isolates of this serotype in North American countries&#46; This resistance profile is mainly associated with the spread of <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> plasmid encoded AmpC &#946;-lactamase<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46; <span class="elsevierStyleItalic">S</span>&#46; Heidelberg is also one of the most common <span class="elsevierStyleItalic">Salmonella</span> serovars isolated from poultry and eggs&#44; whose consumption has led to many foodborne infection outbreaks&#46; Infections caused by personto- person transmission or direct contact with infected animals have been rarely reported<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In Argentina&#44; <span class="elsevierStyleItalic">S&#46;</span> Heidelber g isolates are very infrequent among those submitted to the Centro Nacional de Referencia &#40;Mariana Pichel-Instituto Nacional de Enfermedades Infecciosas-ANLIS &#8220;Carlos G&#46; Malbr&#225;n&#8221;-personal communication&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In this study&#44; we characterized oxyimino-cephalosporin resistance in an <span class="elsevierStyleItalic">S&#46;</span> Heidelberg isolate recovered from a diarrheal stool sample of an HIV adult inpatient&#44; in February 2012&#44; in Buenos Aires&#46; Identification was carried out using conventional culture methods&#46; Serotyping was conducted at the Centro Nacional de Salmonella &#40;CNS&#41; in Montevideo&#44; Uruguay&#46; The CNS&#44; housed in the Departamento de Bacteriolog&#237;a y Virolog&#237;a&#44; Instituto de Higiene&#44; Universidad de la Rep&#250;blica&#44; has characterized <span class="elsevierStyleItalic">Salmonella</span> isolates of human&#44; animal&#44; food&#44; feed and environmental origin&#44; voluntarily submitted by several private and public laboratories for the last 60 years in Uruguay&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Minimal Inhibitory Concentrations &#40;MICs&#41; of different antimicrobial agents were determined using broth microdilution testing and interpreted according to the Clinical and Laboratory Standards Institute &#40;CLSI&#41; guidelines<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46; <span class="elsevierStyleItalic">S&#46;</span> Heidelberg was resistant to ampicillin&#44; cephalothin&#44; cefoxitin&#44; ceftriaxone&#44; ceftazidime&#44; intermediate to tetracycline and susceptible to cefepime&#44; imipenem&#44; aztreonam&#44; kanamycin&#44; gentamicin&#44; ciprofloxacin&#44; levofloxacin and cloramphenicol&#46; Phenotypic screening for &#946;-lactamases was performed by synergy tests using amoxicillin&#47;clavulanic acid &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;10<span class="elsevierStyleHsp" style=""></span>&#956;g&#41; and phenyl-boronic acid &#40;300<span class="elsevierStyleHsp" style=""></span>&#956;g&#41;-containing disks&#46; Synergy was observed between phenyl-boronic acid and both ceftazidime and cefotaxime disks&#44; suggesting the presence of an AmpC type &#946;-lactamase&#46; Plasmid DNA was purified according to the <span class="elsevierStyleItalic">Kado</span> and <span class="elsevierStyleItalic">Liu</span> method&#46; A multiplex-PCR assay was conducted to reveal the presence of plasmidencoded <span class="elsevierStyleItalic">ampC</span> alleles<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#44; rendering a 462 bp amplicon&#44; which suggested the presence of a coding gene for a CIT cluster &#946;-lactamase&#46; The following specific primers &#40;5&#8242;-3&#8242;&#41; were used to achieve the complete <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY</span> gene&#58; CMY-F&#58; ATGATGAAAAAATCGTTATGCT and CMY-R&#58; TTATTGCAGCTTTTCAAGAATGCG&#46; The nucleotide sequence of the 1140 bp amplicon obtained corresponded to <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span>&#46; The genetic context of <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> was determined by PCR mapping and sequencing&#44; as shown in <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#44; using the following primers &#40;5&#8242;-3&#8242;&#41;&#58; TNF&#58; ACCTAGATTCTACGTCAGTACT&#44; AmpC-R&#58; CCCTGGTAGATAACGGCA&#44; Blc-F&#58; CATTCCTGGTTGTCGCGTGT&#44; SugE-F&#58; AGCATGGCGATACTGACGAT&#44; SugE-R&#58; GCCTGATATGTCCTGGATCGT&#44; EcnR-R&#58; GGATTGAGAGGGCACGAT&#46; IS<span class="elsevierStyleItalic">Ecp1</span> was located upstream <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span>&#44; and <span class="elsevierStyleItalic">blc&#44; sugE</span> and <span class="elsevierStyleItalic">ecnR</span> were identified downstream &#40;Accession number HG931731&#41;&#46; The analyzed <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> context agrees completely with the conserved regions reported for Type I&#44; II and III environments described in <span class="elsevierStyleItalic">S&#46; enterica</span>&#44; in which <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> gene is associated with the insertion sequence IS<span class="elsevierStyleItalic">Ecp1</span>&#44; which could enhance <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> expression and mobilization<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Replicon type of <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> harboring plasmid was determined according to Carattoli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#44; corresponding to the IncN group&#46; Plasmid size was estimated in 97 kb by PFGE analysis of S1 nuclease digested DNA<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; Conjugation assays were carried out using <span class="elsevierStyleItalic">E&#46; coli</span> J53 &#40;sodic azid resistant&#41; as recipient strain and Luria Bertani agar plates supplemented with sodium azide &#40;150<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#41; and ceftadizime &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#41; as selection system&#46; <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> plasmid could not be transferred by conjugation in the assayed conditions&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Multilocus sequence typing &#40;MLST&#41; with seven housekeeping genes &#40;<span class="elsevierStyleItalic">aro</span>C&#44; <span class="elsevierStyleItalic">dna</span>N&#44; <span class="elsevierStyleItalic">hem</span>D&#44; <span class="elsevierStyleItalic">his</span>D&#44; <span class="elsevierStyleItalic">pur</span>E&#44; <span class="elsevierStyleItalic">suc</span>A&#44; <span class="elsevierStyleItalic">thr</span>A&#41; was conducted according to <a id="intr0005" class="elsevierStyleInterRef" href="http://mlst.ucc.ie/mlst/dbs/Senterica">http&#58;&#47;&#47;mlst&#46;ucc&#46;ie&#47;mlst&#47;dbs&#47;Senterica</a>&#46; The isolate displayed the following allelic profile&#58; 2&#44; 7&#44; 9&#44; 9&#44; 5&#44; 9&#44; 12&#44; which corresponds to ST 15&#44; as well as the majority of the <span class="elsevierStyleItalic">S&#46;</span> Heidelberg isolates deposited in the MLST database&#46; According to the <span class="elsevierStyleItalic">S&#46; enterica</span> MLST database&#44; ST 15 was more often reported in Europe&#44; North America and Asia&#44; however there is only one description in Africa and two in South America <a id="intr0010" class="elsevierStyleInterRef" href="http://mlst.ucc.ie/mlst/mlst/dbs/Senterica/">http&#58;&#47;&#47;mlst&#46;ucc&#46;ie&#47;mlst&#47;mlst&#47;dbs&#47;Senterica&#47;</a>&#46;<a name="p32"></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Based on the ST analysis&#44; in 2012&#44; <span class="elsevierStyleItalic">S&#46; enterica</span> isolates were grouped together in 138 discrete genetically related clusters called eBurstGroups &#40;eBGs&#41;&#46; Some eBGs exhibit a unique oneto-one relationship with serovars such as eBG26 and <span class="elsevierStyleItalic">S&#46;</span> Heidelberg &#40;<a id="intr0015" class="elsevierStyleInterRef" href="http://mlst.ucc.ie/mlst/mlst/dbs/Senterica/">http&#58;&#47;&#47;mlst&#46;ucc&#46;ie&#47;mlst&#47;mlst&#47;dbs&#47;Senterica&#47;</a>&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Virotyping was performed by PCR amplification of coding genes for proteins secreted by type III secretion systems &#40;<span class="elsevierStyleItalic">avr</span>A&#44; <span class="elsevierStyleItalic">sop</span>E&#41;&#44; <span class="elsevierStyleItalic">Salmonella</span> Typhimurium genomic island CS54 &#40;<span class="elsevierStyleItalic">shd</span>A&#41; and phage encoded genes &#40;<span class="elsevierStyleItalic">gog</span>B and <span class="elsevierStyleItalic">sb</span>41&#41;&#59; specific primers for <span class="elsevierStyleItalic">inv</span>A were included as an internal control<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46; Among the virulence-related genes investigated by PCR amplification&#44; only <span class="elsevierStyleItalic">sop</span>E was detected&#46; The <span class="elsevierStyleItalic">sopE</span> gene encodes for a Rho- GTPase that induces membrane ruffling and elicits a proinfl ammatory response in epithelial cells&#46; The cytosolic localization of SopE in the absence of other bacterial molecules is sufficient for inducing NF-&#954;B activation<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Although there is a national network of laboratories that conducts an exhaustive surveillance of diarrheal episodes&#44; reports of <span class="elsevierStyleItalic">Salmonella</span> spp&#46; infections are not mandatory&#44; except for <span class="elsevierStyleItalic">S</span>&#46; Typhi&#46; It is estimated that only 5&#37; of salmonellosis infections are registered&#46; According to national reports <span class="elsevierStyleItalic">S</span>&#46; Typhimurium and <span class="elsevierStyleItalic">S</span>&#46; Enteriditis constitute the most prevalent serotypes&#44; being <span class="elsevierStyleItalic">S</span>&#46; Heiderberg only sporadically reported&#46; There are no reported data about extended-spectrum cephalosporin resistance among human <span class="elsevierStyleItalic">S</span>&#46; Heidelberg isolates in Argentina&#46; Here we report the first CMY-2-producing <span class="elsevierStyleItalic">S</span>&#46; Heiderberg human isolate in our country&#44; an even in South America&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> gene&#44; constitutes the most common marker among extended-spectrum cephalosporin-resistant <span class="elsevierStyleItalic">Salmonella</span> in the United States&#44; mainly mediated by the spread of IncI1 <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> plasmid<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; This replicon type plasmid has also been described in <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> producing <span class="elsevierStyleItalic">S</span>&#46; Typhimurium isolated from children with diarrhea in Uruguay<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46; More recently IncA&#47;C plasmids have been associated with <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> bovine isolates of <span class="elsevierStyleItalic">S</span>&#46; Heidelberg<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46; However&#44; in the studied isolate <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> was located in an IncN plasmid&#44; this replicon type has not been previously associated to <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> in <span class="elsevierStyleItalic">Salmonella</span> spp&#46; Even in previous studies performed in <span class="elsevierStyleItalic">E&#46; coli</span> in Argentina&#44; where we reported the association of <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> with IncA&#47;C&#44; IncI1&#44; IncFIA&#47;FI&#44; IncK&#44; IncF&#44; IncY and IncBO plasmids&#44; the IncN group was not detected<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Considering the wide diversity of Inc&#47;<span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> associations&#44; the spread of <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> may be related to the presence of a transposable element responsible for its mobilization&#46; Additionally&#44; the co-mobilization of <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> and <span class="elsevierStyleItalic">sugE</span> increases the possibility of co-selection processes&#46; SugE is a member of the small multidrug resistance &#40;SMR&#41; transporter family&#44; responsible for conferring resistance to antiseptics such as quaternary ammonium compounds and SDS<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The spread of resistance markers among <span class="elsevierStyleItalic">S&#46;</span> Heidelberg isolates constitutes a risk for the management of severe salmonellosis in clinical practice&#46; Therefore&#44; a better understanding of the pathogen distribution and its antimicrobial resistance is important for the development of strategies to limit salmonellosis due to multidrugresistant strains&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Ethical responsibilities</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Protection of human and animal subjects</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Confidentiality of data</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Right to privacy and informed consent</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article&#46;</p></span></span></span>"
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              "titulo" => "Protection of human and animal subjects"
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              "titulo" => "Confidentiality of data"
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              "titulo" => "Right to privacy and informed consent"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Salmonella enterica</span> serovar Heidelberg ranks among the most prevalent causes of human salmonellosis in the United States and Canada&#44; although it has been infrequently reported in South American and European countries&#46; Most <span class="elsevierStyleItalic">Salmonella</span> infections are self-limiting&#59; however&#44; some invasive infections require antimicrobial therapy&#46; In this work we characterized an oxyimino-cephalosporin resistant <span class="elsevierStyleItalic">S&#46;</span> Heidelberg isolate recovered from an inpatient in a Buenos Aires hospital&#46; CMY-2 was responsible for the &#946;-lactam resistance profile&#46; <span class="elsevierStyleItalic">S&#46;</span> Heidelberg contained a 97<span class="elsevierStyleHsp" style=""></span>kb plasmid belonging to the Inc N group harboring <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span>&#46; IS<span class="elsevierStyleItalic">Ecp1</span> was located upstream <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> driving its expression and mobilization&#46; The isolate belonged to sequence type 15 and virotyping revealed the presence of <span class="elsevierStyleItalic">sopE</span> gene&#46; In this study we identified the first CMY-2 producing isolate of <span class="elsevierStyleItalic">S&#46;</span> Heidelberg in Argentina and even in South America&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Salmonella enterica</span> serovar Heidelberg es uno de los principales agentes causantes de salmonelosis en humanos en Estados Unidos y Canad&#225;&#44; sin embargo&#44; resulta infrecuente en los pa&#237;ses de Sudam&#233;rica y Europa&#46; En este trabajo se caracteriz&#243; un aislamiento de <span class="elsevierStyleItalic">S&#46;</span> Heidelberg resistente a oximino-cefalosporinas recuperado de un paciente internado<a name="p31"></a> en un hospital de la Ciudad de Buenos Aires&#46; Se evidenci&#243; la presencia de un pl&#225;smido de 97<span class="elsevierStyleHsp" style=""></span>kb perteneciente al grupo de incompatibilidad IncN&#44; portador del gen <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span>&#46; IS<span class="elsevierStyleItalic">Ecp1</span> fue localizado corriente arriba de <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span>&#44; promoviendo su expresi&#243;n y movilizaci&#243;n&#46; El aislamiento de <span class="elsevierStyleItalic">S&#46;</span> Heidelberg correspondi&#243; al secuenciotipo 15 y en la virotipificaci&#243;n se detect&#243; el gen <span class="elsevierStyleItalic">sopE</span>&#46; En este trabajo describimos por primera vez la producci&#243;n de CMY-2 en una cepa de <span class="elsevierStyleItalic">S&#46;</span> Heidelberg en nuestro pa&#237;s y Am&#233;rica Latina&#46;</p></span>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Genetic context of <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span>&#46; ISE<span class="elsevierStyleItalic">cp1</span>&#58; Insertion sequence <span class="elsevierStyleItalic">Ecp1&#44; blc</span>&#58; gene encoding for outer membrane lipoprotein&#44;&#40;lipocalin&#41;&#59; <span class="elsevierStyleItalic">sugE</span>&#58; gene encoding for small multidrug resistance protein&#59; <span class="elsevierStyleItalic">ecnR</span>&#58; coding gene for a transcriptional regulatory protein&#44; entericidinR&#46;</p>"
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:15 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genetic characterization of clinical and agri-food isolates of multi drug resistant <span class="elsevierStyleItalic">Salmonella enterica</span> serovar Heidelberg from Canada"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:7 [
                            0 => "A&#46;K&#46; Andrysiak"
                            1 => "A&#46;B&#46; Olson"
                            2 => "D&#46;M&#46; Tracz"
                            3 => "K&#46; Dore"
                            4 => "R&#46; Irwin"
                            5 => "L&#46;K&#46; Ng"
                            6 => "M&#46;W&#46; Gilmour"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1471-2180-8-89"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Microbiol"
                        "fecha" => "2008"
                        "volumen" => "8"
                        "paginaInicial" => "89"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18538029"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Identification of plasmids by PCR-based replicon typing"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Carattoli"
                            1 => "A&#46; Bertini"
                            2 => "L&#46; Villa"
                            3 => "V&#46; Fal bo"
                            4 => "K&#46;L&#46; Hopkins"
                            5 => "E&#46;J&#46; Threlfall"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.mimet.2005.03.018"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Microbiol Methods"
                        "fecha" => "2005"
                        "volumen" => "63"
                        "paginaInicial" => "219"
                        "paginaFinal" => "228"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15935499"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Resistance plasmid fami lies in <span class="elsevierStyleItalic">Enterobacteriaceae</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "A&#46; Carattoli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/AAC.01707-08"
                      "Revista" => array:6 [
                        "tituloSerie" => "Antimicrob Agents Chemother"
                        "fecha" => "2009"
                        "volumen" => "53"
                        "paginaInicial" => "2227"
                        "paginaFinal" => "2238"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19307361"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Plasmid-encoded AmpC &#40;pAmpC&#41; in <span class="elsevierStyleItalic">Enterobacteriaceae</span>&#58; epidemiology of microorganisms and resistance markers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:11 [
                            0 => "D&#46; Cejas"
                            1 => "L&#46; Fern&#225;ndez Canigia"
                            2 => "M&#46; Quinte ros"
                            3 => "M&#46; Giovanakis"
                            4 => "C&#46; Vay"
                            5 => "S&#46; Lascialandare"
                            6 => "D&#46; Mutti"
                            7 => "G&#46; Pagniez"
                            8 => "M&#46; Almuzara"
                            9 => "G&#46; Gutkind"
                            10 => "M&#46; Radice"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Argent Microbiol"
                        "fecha" => "2012"
                        "volumen" => "44"
                        "paginaInicial" => "182"
                        "paginaFinal" => "186"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23102467"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Clinical and Laboratory Standards In stitute&#58; Performance standards for antimicrobial susceptibility testing&#59; 22nd informational supplement&#44; 2012&#59; M100-S22&#46; Wayne&#44; PA&#44; USA&#46;"
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Identification of the first <span class="elsevierStyleItalic">bla</span><span class="elsevierStyleInf">CMY-2</span> gene in <span class="elsevierStyleItalic">Salmonella enterica</span> serovar Typhimurium isolates obtained from cases of paediatric diarrhoea illness detected in South America"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:12 [
                            0 => "Y&#46;L&#46; Cordeiro Nicol&#225;s"
                            1 => "L&#46; Betancor"
                            2 => "D&#46; Cej as"
                            3 => "V&#46; Garc&#237;a-Fulgueiras"
                            4 => "M&#46; Mota"
                            5 => "G&#46; Varela"
                            6 => "L&#46; Anzalone"
                            7 => "G&#46; Algorta"
                            8 => "G&#46; Gutkind"
                            9 => "J&#46; Ayala"
                            10 => "J&#46; Chabalgoity"
                            11 => "R&#46; Vignoli"
                          ]
                        ]
                      ]
                    ]
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        "texto" => "<p id="par0095" class="elsevierStylePara elsevierViewall">This work was partially supported by Grants from UBACyT and ANPCyT to M&#46; Radice and G&#46; Gutkind&#46; G&#46; Gutkind and M&#46; Radice are members of Carrera del Investigador Cient&#237;fico &#40;CONICET&#41;&#46; D&#46; Cejas was recipient of a doctoral fellowship from CONICET and is now recipient of a postdoctoral fellowship from Fundaci&#243;n Bunge y Born&#46;</p> <p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Conflicts of interest</span></p> <p id="par0090" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p>"
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

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Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos