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Open AccessArticle

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

1
Microbiology Department-Research Institute Biomedical A Coruña (INIBIC), Hospital A Coruña (CHUAC), University of A Coruña (UDC), 15006 A Coruña, Spain
2
Study Group on Mechanisms of Action and Resistance to Antimicrobials (GEMARA) the Behalf of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), 28003 Madrid, Spain
3
Clinical Unit for Infectious Diseases, Department of Microbiology and Medicine, Microbiology and Preventive Medicine, Hospital Universitario Virgen Macarena, University of Seville, Biomedicine Insititute of Seville (IBIS), 41009 Seville, Spain
4
Spanish Network for Research in Infectious Diseases (REIPI), 41071 Seville, Spain
5
Reference and Research Laboratory for Antibiotic Resistance and Health Care Infections, National Centre for Microbiology, Institute of Health Carlos III, 28222 Majadahonda, Spain
6
Department of Chemical Engineering, Pennsylvania State University, University Park, PA 16801, USA
*
Author to whom correspondence should be addressed.
These authors equally contributed to this work.
Toxins 2020, 12(9), 566; https://doi.org/10.3390/toxins12090566
Received: 23 July 2020 / Revised: 28 August 2020 / Accepted: 29 August 2020 / Published: 2 September 2020
(This article belongs to the Special Issue Toxin-Antitoxin Systems in Pathogenic Bacteria)
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). View Full-Text
Keywords: tolerance; persistence; cross-resistance; toxin-antitoxin system; PemI/PemK; Klebsiella pneumoniae tolerance; persistence; cross-resistance; toxin-antitoxin system; PemI/PemK; Klebsiella pneumoniae
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MDPI and ACS Style

Bleriot, I.; Blasco, L.; Delgado-Valverde, M.; Gual-de-Torrella, 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. https://doi.org/10.3390/toxins12090566

AMA Style

Bleriot I, Blasco L, Delgado-Valverde M, Gual-de-Torrella A, Ambroa A, Fernandez-Garcia L, Lopez M, Oteo-Iglesias J, Wood TK, 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(9):566. https://doi.org/10.3390/toxins12090566

Chicago/Turabian Style

Bleriot, Ines; Blasco, Lucia; Delgado-Valverde, Mercedes; Gual-de-Torrella, Ana; Ambroa, Anton; Fernandez-Garcia, Laura; Lopez, Maria; Oteo-Iglesias, Jesus; Wood, Thomas K.; Pascual, Alvaro; Bou, German; Fernandez-Cuenca, Felipe; Tomas, Maria. 2020. "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 12, no. 9: 566. https://doi.org/10.3390/toxins12090566

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