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Title

Mechanisms of Tolerance and Resistance to Chlorhexidine in Clinical Strains of Klebsiella pneumoniae Producers of Carbapenemase: Role of New Type II Toxin-Antitoxin System, PemIK

AuthorsBleriot, Inés; Blasco, Lucía; Delgado-Valverde, Mercedes; Gual-de-Torrella, Ana; Ambroa, Antón; Fernández-García, Laura; López, María; Oteo, Jesús; Wood, Thomas K.; Pascual, Álvaro; Bou, Germán; Fernández-Cuenca, Felipe; Tomás, María
KeywordsTolerance
Persistence
Cross-resistance
Toxin-antitoxin system
PemI/PemK
Klebsiella pneumoniae
Issue Date2-Sep-2020
PublisherMultidisciplinary Digital Publishing Institute
CitationToxins 12(9): 566 (2020)
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).
DescriptionThis article belongs to the Special Issue Toxin-Antitoxin Systems in Pathogenic Bacteria.
Publisher version (URL)http://doi.org/10.3390/toxins12090566
URIhttp://hdl.handle.net/10261/235280
Identifiersdoi: 10.3390/toxins12090566
e-issn: 2072-6651
Appears in Collections:(IBIS) Artículos
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