ArticleAntimicrobial agents and chemotherapy2016
Amino Acid Substitutions of CrrB Responsible for Resistance to Colistin through CrrC in Klebsiella pneumoniae.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Systematic review and meta-analysis of colistin heteroresistance in Klebsiella pneumoniae isolates.BMC infectious diseases · 2025Pooled it
- A posttranslational modification of fimbriae drives pathogenicity inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Overview of Colistin Resistance in the Middle East and North Africa (MENA) Region.Microorganisms · 2026Review
- Molecular analysis of polymyxin B resistance in clinical carbapenem-resistant Klebsiella pneumoniae isolates from a large tertiary care teaching hospital in Southwest China.BMC microbiology · 2026Article
- Within-host mechanisms of resistance evolution in polymyxin B-resistant Klebsiella pneumoniae without prior exposure.Annals of clinical microbiology and antimicrobials · 2026Article
- Molecular evaluation of colistin resistance inIranian journal of microbiology · 2026Article
- Carbapenem and colistin-resistantJAC-antimicrobial resistance · 2026Article
- Antibiotic Resistance inAntibiotics (Basel, Switzerland) · 2026Review
- Colistin Resistance in Bacteria: Current Updates on Mechanism of Action and Combating Strategies.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2026Review
- A novel post-translational modification of fimbriae drives pathogenicity inbioRxiv : the preprint server for biology · 2025Article
- How Klebsiella pneumoniae controls its virulence.PLoS pathogens · 2025Review
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- Article
- Rapid evolution of colistin resistance in a bioreactor model of infection of Klebsiella pneumoniae.Communications biology · 2024Article
- Colistin: Lights and Shadows of an Older Antibiotic.Molecules (Basel, Switzerland) · 2024Review
- Influence of PhoPQ and PmrAB two component system alternations on colistin resistance from non-mcr colistin resistant clinical E. Coli strains.BMC microbiology · 2024Article
- Synergistic effects of polymyxin and vancomycin combinations on carbapenem- and polymyxin-resistantMicrobiology spectrum · 2023Article
- Heteroresistance to Colistin in Clinical Isolates ofAntibiotics (Basel, Switzerland) · 2023Article
- Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps.Antibiotics (Basel, Switzerland) · 2023Review
- Missense Mutations in the CrrB Protein Mediate Odilorhabdin Derivative Resistance inAntimicrobial agents and chemotherapy · 2023Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colistin is a last-resort antibiotic for treatment of carbapenem-resistant Klebsiella pneumoniae A recent study indicated that missense mutations in the CrrB protein contribute to colistin resistance. In our previous study, mechanisms of colistin resistance were defined in 17 of 26 colistin-resistant K. pneumoniae clinical isolates. Of the remaining nine strains, eight were highly resistant to colistin. In the present study, crrAB sequences were determined for these eight strains. Six separate amino acid substitutions in CrrB (Q10L, Y31H, W140R, N141I, P151S, and S195N) were detected. Site-directed mutagenesis was used to generate crrB loci harboring individual missense mutations; introduction of the mutated genes into a susceptible strain, A4528, resulted in 64- to 1,024-fold increases in colistin MICs. These crrB mutants showed increased accumulation of H239_3062, H239_3059, pmrA, pmrC, and pmrH transcripts by quantitative reverse transcription (qRT)-PCR. Deletion of H239_3062 (but not that of H239_3059) in the A4528 crrB(N141I) strain attenuated resistance to colistin, and H239_3062 was accordingly named crrC Similarly, accumulation of pmrA, pmrC, and pmrH transcripts induced by crrB(N141I) was significantly attenuated upon deletion of crrC Complementation of crrC restored resistance to colistin and accumulation of pmrA, pmrC, and pmrH transcripts in a crrB(N141I) ΔcrrC strain. In conclusion, novel individual CrrB amino acid substitutions (Y31H, W140R, N141I, P151S, and S195N) were shown to be responsible for colistin resistance. We hypothesize that CrrB mutations induce CrrC expression, thereby inducing elevated expression of the pmrHFIJKLM operon and pmrC (an effect mediated via the PmrAB two-component system) and yielding increased colistin resistance.
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