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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
Authors: Bleriot, Ines
Blasco, Lucia
Delgado-Valverde, Mercedes
Gual-de-Torella, Ana
Ambroa, Anton
Fernandez-Garcia, Laura
Lopez, Maria
Oteo-Iglesias, Jesus
Wood, Thomas K.
Pascual, Alvaro
Bou, German
Fernandez-Cuenca, Felipe
Tomas, Maria
metadata.dc.contributor.authoraffiliation: [Bleriot,I; Blasco,L; Ambroa,A; Fernandez-Garcia,L; Lopez,M; Bou,G; Tomas,M] Microbiology Department-Research Institute Biomedical A Coruña (INIBIC), Hospital A Coruña (CHUAC), University of A Coruña (UDC), A Coruña, Spain. [Bleriot,I; Blasco,L; Fernandez-Garcia,L; Oteo-Iglesias,J; Pascual,A; Bou,G; Fernandez-Cuenca,F; Tomas,M] Study Group on Mechanisms of Action and Resistance to Antimicrobials (GEMARA) the Behalf of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), Madrid, Spain. [Delgado-Valverde,M; Gual-de-Torella,A; Pascual,A; Fernandez-Cuenca,F] 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), Seville, Spain. [Lopez,M; Oteo-Iglesias,J; Pascual,A; Bou,G; Fernandez-Cuenca,F; Tomas,M] Spanish Network for Research in Infectious Diseases (REIPI), Seville, Spain. [Oteo-Iglesias,J] Reference and Research Laboratory for Antibiotic Resistance and Health Care Infections, National Centre for Microbiology, Institute of Health Carlos III, Majadahonda, Spain. [Wood,TK] Department of Chemical Engineering, Pennsylvania State University, University Park, PA, USA.
Keywords: Tolerance;Persistence;Cross-resistance;Toxin-antitoxin system;PemI/PemK;Klebsiella pneumoniae;Combinación de medicamentos;Farmacorresistencia bacteriana;Sistemas toxina-antitoxina;Transcriptoma
metadata.dc.subject.mesh: Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Infective Agents, Local
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Bacterial Proteins
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amidines::Guanidines::Biguanides::Chlorhexidine
Medical Subject Headings::Chemicals and Drugs::Pharmaceutical Preparations::Drug Combinations
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Pharmacological Processes::Drug Tolerance
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Carbapenems::Thienamycins::Imipenem
Medical Subject Headings::Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Facultatively Anaerobic Rods::Enterobacteriaceae::Klebsiella::Klebsiella pneumoniae
Medical Subject Headings::Phenomena and Processes::Physical Phenomena::Time::Time Factors
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases::beta-Lactamases
Medical Subject Headings::Phenomena and Processes::Microbiological Phenomena::Bacterial Physiological Phenomena::Drug Resistance, Bacterial
Toxin-Antitoxin Systems
Issue Date: 2-Sep-2020
Publisher: MDPI
Citation: Bleriot I, Blasco L, Delgado-Valverde M, Gual de Torella A, Ambroa A, Fernandez-Garcia L, et al. 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 Sep 2;12(9):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 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).
metadata.dc.identifier.doi: 10.3390/toxins12090566
ISSN: 2072-6651 (Online)
Appears in Collections:01- Artículos - Hospital Virgen Macarena
01- Artículos - IBIS. Instituto de Biomedicina de Sevilla

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