Publication:
Clinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterization

dc.contributor.authorRivero-Menendez, Olga
dc.contributor.authorNavarro-Rodriguez, Patricia
dc.contributor.authorBernal-Martinez, Leticia
dc.contributor.authorMartin-Cano, Gema
dc.contributor.authorLopez-Perez, Laura
dc.contributor.authorSanchez-Romero, Isabel
dc.contributor.authorPerez-Ayala, Ana
dc.contributor.authorCapilla, Javier
dc.contributor.authorZaragoza, Oscar
dc.contributor.authorAlastruey-Izquierdo, Ana
dc.contributor.funderInstituto de Salud Carlos III
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España)
dc.contributor.funderRETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España)
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
dc.date.accessioned2020-02-21T10:55:43Z
dc.date.available2020-02-21T10:55:43Z
dc.date.issued2019
dc.description.abstractThe pathogenic yeast Candida glabrata has become a public health issue due to the increasing number of echinocandin resistant clinical strains reported. In this study, acquisition and development of resistance to this antifungal class were studied in serial C. glabrata isolates from five patients admitted in two Spanish hospitals with a resistant profile against echinocandins associated with different mutations in hot-spot 1 of FKS2 gene. For two of these patients susceptible FKS wild-type isolates obtained prior to resistant ones were also investigated. Isolates were genotyped using multilocus sequence typing and microsatellite length polymorphism techniques, which yielded comparable results. Susceptible and resistant isolates from the same patient had the same genotype, being sequence type (ST) 3 the most prevalent among them. Isolates with different FKS mutations but the same ST were present in the same patient. MSH2 gene alterations were also studied to investigate their correlation with antifungal resistance acquisition but no association was found with antifungal resistance nor with specific genotypes. In vitro exposure to increasing concentrations of micafungin to susceptible isolates developed colonies carrying FKS mutations in agar plates containing a minimum concentration of 0.06 mg/L of micafungin after less than 48 h of exposure. We investigated the correlation between development of resistance and genotype in a set of susceptible strains after being in vitro exposed to micafungin and anidulafungin but no correlation was found. Mutant prevention concentration values and spontaneous growth frequencies after selection with both echinocandins were statistically similar, although FKS mutant colonies were more abundant after micafungin exposure (p < 0.001). Mutation S663P and F659 deletion were the most common ones found after selection with both echinocandins.es_ES
dc.description.peerreviewedes_ES
dc.description.sponsorshipThis work was supported by the Fondo de Investigación Sanitaria (Grant FI14CIII/00025 to OR-M and research projects PI13/02145 and PI16CIII/00035 to AA-I), and also supported by the Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16CIII/0004/0003) – co-financed by the European Development Regional Fund “A way to achieve Europe,” Operative Program Intelligent Growth 2014–2020.es_ES
dc.format.page1585es_ES
dc.format.volume10es_ES
dc.identifier.citationFront Microbiol. 2019 Jul 11;10:1585.es_ES
dc.identifier.doi10.3389/fmicb.2019.01585es_ES
dc.identifier.issn1664-302Xes_ES
dc.identifier.journalFrontiers in microbiologyes_ES
dc.identifier.pubmedID31354675es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/9118
dc.language.isoenges_ES
dc.publisherFrontiers Mediaes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FI14CIII/00025es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI13/02145es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI16CIII/00035es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/REIPI RD16CIII/0004/0003es_ES
dc.relation.publisherversionhttps://doi.org/10.3389/fmicb.2019.01585es_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCandida glabrataes_ES
dc.subjectFKSes_ES
dc.subjectMSH2es_ES
dc.subjectanidulafungines_ES
dc.subjectantifungal resistancees_ES
dc.subjectechinocandinses_ES
dc.subjectgenotypinges_ES
dc.subjectmicafungines_ES
dc.titleClinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterizationes_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
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