RT Journal Article
T1 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
A1 Bleriot, Ines
A1 Blasco, Lucia
A1 Delgado-Valverde, Mercedes
A1 Gual-de-Torella, Ana
A1 Ambroa, Anton
A1 Fernandez-Garcia, Laura
A1 Lopez, Maria
A1 Oteo-Iglesias, Jesus
A1 Wood, Thomas K.
A1 Pascual, Alvaro
A1 Bou, German
A1 Fernandez-Cuenca, Felipe
A1 Tomas, Maria
K1 Tolerance
K1 Persistence
K1 Cross-resistance
K1 Toxin-antitoxin system
K1 PemI/PemK
K1 Klebsiella pneumoniae
K1 Combinación de medicamentos
K1 Farmacorresistencia bacteriana
K1 Sistemas toxina-antitoxina
K1 Transcriptoma
AB 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).
PB MDPI
YR 2020
FD 2020-09-02
LK http://hdl.handle.net/10668/3709
UL http://hdl.handle.net/10668/3709
LA en
NO Bleriot I, Blasco L, Delgado-Valverde M, Gual de Torella A, Ambroa A, Fernandez-Garcia L, et al. 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. Toxins. 2020 Sep 2;12(9):566
DS RISalud
RD Apr 7, 2025