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dc.contributor.authorBleriot, Ines
dc.contributor.authorBlasco, Lucia
dc.contributor.authorDelgado-Valverde, Mercedes
dc.contributor.authorGual de Torella, Ana
dc.contributor.authorAmbroa, Anton
dc.contributor.authorFernandez-Garcia, Laura
dc.contributor.authorLopez, Maria
dc.contributor.authorOteo-Iglesias, Jesus 
dc.contributor.authorWood, Thomas K
dc.contributor.authorPascual, Alvaro
dc.contributor.authorBou, German
dc.contributor.authorFernández-Cuenca, Felipe
dc.contributor.authorTomas, Maria
dc.date.accessioned2020-11-24T10:27:18Z
dc.date.available2020-11-24T10:27:18Z
dc.date.issued2020-09-02
dc.identifier.citationToxins (Basel). 2020 Sep 2;12(9):566.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/11407
dc.description.abstractAlthough the failure of antibiotic treatment is normally attributed to resistance, tolerance and persistence display a significant role in the lack of response to antibiotics. Due to the fact that several nosocomial pathogens show a high level of tolerance and/or resistance to chlorhexidine, in this study we analyzed the molecular mechanisms associated with chlorhexidine adaptation in two clinical strains of Klebsiella pneumoniae by phenotypic and transcriptomic studies. These two strains belong to ST258-KPC3 (high-risk clone carrying β-lactamase KPC3) and ST846-OXA48 (low-risk clone carrying β-lactamase OXA48). Our results showed that the K. pneumoniae ST258-KPC3CA and ST846-OXA48CA strains exhibited a different behavior under chlorhexidine (CHLX) pressure, adapting to this biocide through resistance and tolerance mechanisms, respectively. Furthermore, the appearance of cross-resistance to colistin was observed in the ST846-OXA48CA strain (tolerant to CHLX), using the broth microdilution method. Interestingly, this ST846-OXA48CA isolate contained a plasmid that encodes a novel type II toxin/antitoxin (TA) system, PemI/PemK. We characterized this PemI/PemK TA system by cloning both genes into the IPTG-inducible pCA24N plasmid, and found their role in persistence and biofilm formation. Accordingly, the ST846-OXA48CA strain showed a persistence biphasic curve in the presence of a chlorhexidine-imipenem combination, and these results were confirmed by the enzymatic assay (WST-1).es_ES
dc.description.sponsorshipThis study was funded by grants PI16/01163 and PI19/00878 awarded to M. Tomás within the State Plan for R+D+I 2013–2016 (National Plan for Scientific Research, Technological Development and Innovation 2008–2011) and co-financed by the ISCIII-Deputy General Directorate for Evaluation and Promotion of Research - European Regional Development Fund “A way of Making Europe” and Instituto de Salud Carlos III FEDER, Spanish Network for the Research in Infectious Diseases (REIPI, RD16/0016/0001, RD16/CIII/0004/0002 and RD16/0016/0006) and by the Study Group on Mechanisms of Action and Resistance to Antimicrobials, GEMARA (SEIMC, http://www.seimc.org/).es_ES
dc.language.isoenges_ES
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectKlebsiella pneumoniaees_ES
dc.subjectCross-resistancees_ES
dc.subjectPersistencees_ES
dc.subjectTolerancees_ES
dc.subjectToxin-antitoxin systemes_ES
dc.titleMechanisms of Tolerance and Resistance to Chlorhexidine in Clinical Strains of Klebsiella pneumoniae Producers of Carbapenemase: Role of New Type II Toxin-Antitoxin System, PemIKes_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID32887507es_ES
dc.format.volume12es_ES
dc.format.number9es_ES
dc.identifier.doi10.3390/toxins12090566es_ES
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderRETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España) 
dc.description.peerreviewedes_ES
dc.identifier.e-issn2072-6651
dc.relation.publisherversionhttps://doi.org/10.3390/toxins12090566es_ES
dc.identifier.journalToxinses_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI16/01163es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI19/00878es_ES
dc.rights.accessRightsopen accesses_ES


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