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oai:repisalud.isciii.es:20.500.12105/114072025-05-05T15:03:56Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16958col_20.500.12105_16985

00925njm 22002777a 4500 dc Bleriot, Ines author Blasco, Lucia author Delgado-Valverde, Mercedes author Gual de Torella, Ana author Ambroa, Antón author Fernández-García, Laura author Lopez, Maria author Oteo-Iglesias, Jesus author Wood, Thomas K author Pascual, Álvaro author Bou, Germán author Fernández-Cuenca, Felipe author Tomas, Maria author 2020-09-02 Although 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). Toxins (Basel). 2020 Sep 2;12(9):566. 10.3390/toxins12090566 2072-6651 Toxins 32887507 http://hdl.handle.net/20.500.12105/11407 Klebsiella pneumoniae Cross-resistance Persistence Tolerance Toxin-antitoxin system 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