Cited by 313Antibiotic Resistance in BacteriaBacterial Genetics and BiotechnologyAntimicrobial agents and applications

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Mechanisms of Increased Resistance to Chlorhexidine and Cross-Resistance to Colistin following Exposure of Klebsiella pneumoniae Clinical Isolates to Chlorhexidine

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Wand, Matthew E., Bock, Lucy J., Bonney, Laura C., Sutton, J. Mark·2017·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.01162-16PMC PMC5192135

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Abstract

Klebsiella pneumoniae is an opportunistic pathogen that is often difficult to treat due to its multidrug resistance (MDR). We have previously shown that K. pneumoniae strains are able to “adapt” (become more resistant) to the widely used bisbiguanide antiseptic chlorhexidine. Here, we investigated the mechanisms responsible for and the phenotypic consequences of chlorhexidine adaptation, with particular reference to antibiotic cross-resistance. In five of six strains, adaptation to chlorhexidine also led to resistance to the last-resort antibiotic colistin. Here, we show that chlorhexidine adaptation is associated with mutations in the two-component regulator phoPQ and a putative Tet repressor gene ( smvR ) adjacent to the major facilitator superfamily (MFS) efflux pump gene, smvA . Upregulation of smvA (10- to 27-fold) was confirmed in smvR mutant strains, and this effect and the associated phenotype were suppressed when a wild-type copy of smvR was introduced on plasmid pACYC. Upregulation of phoPQ (5- to 15-fold) and phoPQ -regulated genes, pmrD (6- to 19-fold) and pmrK (18- to 64-fold), was confirmed in phoPQ mutant strains. In contrast, adaptation of K. pneumoniae to colistin did not result in increased chlorhexidine resistance despite the presence of mutations in phoQ and elevated phoPQ , pmrD , and pmrK transcript levels. Insertion of a plasmid containing phoPQ from chlorhexidine-adapted strains into wild-type K. pneumoniae resulted in elevated expression levels of phoPQ , pmrD , and pmrK and increased resistance to colistin, but not chlorhexidine. The potential risk of colistin resistance emerging in K. pneumoniae as a consequence of exposure to chlorhexidine has important clinical implications for infection prevention procedures.

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Chlorhexidine Digluconate
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Additional file 1 of Mutations in SilS and CusS/OmpC represent different routes to achieve high level silver ion tolerance in Klebsiella pneumoniae
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Self-citation

Authors: Wand, M. E., Bock, L. J., Bonney, L. C., & Sutton, J. M.
Affiliations: Public Health England (GB)
ORCID: Wand, Matthew E.
Bock, Lucy J.
Bonney, Laura C.
Sutton, J. Mark
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2017-01
Volume: 61
Issue: 1
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.01162-16
PMC: PMC5192135
OpenAlex: W2540856562
Cited by: 313
References: 54
Citations by year: 2026: 19 · 2025: 25 · 2024: 23 · 2023: 34 · 2022: 46 · 2021: 43 · 2020: 36 · 2019: 47 · 2018: 19 · 2017: 18
FWCI: 13.87
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Public Health England (GIA 109506)
Topics: Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antimicrobial agents and applications
Keywords: Klebsiella pneumoniae, chlorhexidine, colistin, cross-resistance, PhoPQ two-component system, major facilitator superfamily, multidrug resistance, infection control
MeSH terms: Anti-Bacterial Agents, Bacterial Proteins, Chlorhexidine, Colistin, Klebsiella pneumoniae, Microbial Sensitivity Tests, Mutation, Plasmids, Drug Resistance, Bacterial

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Mechanisms of Increased Resistance to Chlorhexidine and Cross-Resistance to Colistin following Exposure of Klebsiella pneumoniae Clinical Isolates to Chlorhexidine

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