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Mechanisms of Increased Resistance to Chlorhexidine and Cross-Resistance to Colistin following Exposure of Klebsiella pneumoniae Clinical Isolates to Chlorhexidine
Open accessAbstract
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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“Indeed, AMR has become one of the major threats to human health, emerging and spreading, particularly in hospital environments, as a result of the selective pressures exerted by the widespread use of disinfectants and antibiotics in these settings [16].”
From Profiling the resistome and virulome of Bacillus strains used for probiotic-based sanitation: a multicenter WGS analysis (2025) · cites this paper as [16]
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“These include analysing the effects of biocides on membrane integrity of live cells or vesicles and liposomes through the use of microscopy, the uptake of substrates (for example, fluorescent dyes or particles) and the leakage of cellular components (for example,”
Background
Metadata
- Authors
- Wand, M. E., Bock, L. J., Bonney, L. C., & Sutton, J. M.
- Affiliations
- Public Health England (GB)
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2017-01
- Volume
- 61
- Issue
- 1
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- 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
- 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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