Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Whole Transcriptomic Analysis of Mechanisms of Tolerance and Resistance to Chlorhexidine in Clinical Strains of Klebsiella Pneumoniae Producers of Carbapenemase

Version 1 : Received: 23 July 2020 / Approved: 24 July 2020 / Online: 24 July 2020 (11:46:37 CEST)

A peer-reviewed article of this Preprint also exists.

Bleriot, I.; Blasco, L.; Delgado-Valverde, M.; Gual de Torella, A.; Ambroa, A.; Fernandez-Garcia, L.; Lopez, M.; Oteo-Iglesias, J.; Wood, T.K.; Pascual, A.; Bou, G.; Fernandez-Cuenca, F.; Tomas, M. 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, 12, 566. Bleriot, I.; Blasco, L.; Delgado-Valverde, M.; Gual de Torella, A.; Ambroa, A.; Fernandez-Garcia, L.; Lopez, M.; Oteo-Iglesias, J.; Wood, T.K.; Pascual, A.; Bou, G.; Fernandez-Cuenca, F.; Tomas, M. 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, 12, 566.

Journal reference: Toxins 2020, 12, 566
DOI: 10.3390/toxins12090566

Abstract

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 K. pneumoniae ST258-KPC3CA and ST846-OXA48CA strains exhibited a different behavior under 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, PemK/PemI. We characterized this PemK/PemI 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).

Subject Areas

Tolerance; Persistence; Cross-resistance; Toxin-antitoxin system; PemK/PemI; Klebsiella pneumoniae.

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.