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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

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551900/
https://www.ncbi.nlm.nih.gov/pubmed/32887507
http://dx.doi.org/10.3390/toxins12090566
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author 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
author_facet 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
author_sort Bleriot, Ines
collection PubMed
description 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).
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spelling pubmed-75519002020-10-14 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 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 Toxins (Basel) Article 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). MDPI 2020-09-02 /pmc/articles/PMC7551900/ /pubmed/32887507 http://dx.doi.org/10.3390/toxins12090566 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551900/
https://www.ncbi.nlm.nih.gov/pubmed/32887507
http://dx.doi.org/10.3390/toxins12090566
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