Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed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

Ines Bleriot
ORCID logo ,
Lucia Blasco
ORCID logo ,
Mercedes Delgado
,
Ana Gual de Torrella
,
Anton Ambroa
,
Laura Fernandez-Garcia
ORCID logo ,
Maria Lopez-Diaz
,
Jesús Oteo
,
Thomas Wood
ORCID logo ,
Alvaro Pascual
,
Germán Bou
,
Felipe Fernandez-Cuenca
,
Maria Tomas
* ORCID logo
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.

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).

Keywords

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

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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