2026-05-20T19:10:31Zhttps://repisalud.isciii.es/rest/oai/requestoai: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
Repisalud
author
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
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
RETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España)
2020-11-24T10:27:18Z
2020-11-24T10:27:18Z
2020-09-02
Toxins (Basel). 2020 Sep 2;12(9):566.
10.3390/toxins12090566
2072-6651
Toxins
32887507
http://hdl.handle.net/20.500.12105/11407
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).
eng
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
research article
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MechanismsoOFToleranceAnd_2020 Suplementrary Materials.pdf
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MechanismsoOFToleranceAnd_2020.pdf.txt
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