ArticleThe Journal of antimicrobial chemotherapy2018
A putative RND-type efflux pump, H239_3064, contributes to colistin resistance through CrrB in Klebsiella pneumoniae.
Article in The Journal of antimicrobial chemotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
- A posttranslational modification of fimbriae drives pathogenicity inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- The colistin resistance pandemic: A dual threat from plasmid-encoded mobilised colistin resistance genes and chromosomal mutations.African journal of laboratory medicine · 2026Review
- Antibiotic Resistance inAntibiotics (Basel, Switzerland) · 2026Review
- Inhibition of RND-mediated efflux attenuates antibiotic resistance and virulence in hypervirulentInfection and immunity · 2025Article
- A novel post-translational modification of fimbriae drives pathogenicity inbioRxiv : the preprint server for biology · 2025Article
- Review
- Molecular Mechanisms of Bacterial Resistance to Antimicrobial Peptides in the Modern Era: An Updated Review.Microorganisms · 2024Review
- Extending the Potency and Lifespan of Antibiotics: Inhibitors of Gram-Negative Bacterial Efflux Pumps.ACS infectious diseases · 2024Review
- Insights into Kinases of ESKAPE Pathogens for Therapeutic Interventions.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Article
- A Review of Resistance to Polymyxins and Evolving Mobile Colistin Resistance Gene (Antibiotics (Basel, Switzerland) · 2023Review
- Missense Mutations in the CrrB Protein Mediate Odilorhabdin Derivative Resistance inAntimicrobial agents and chemotherapy · 2023Article
- Role of efflux pumps, their inhibitors, and regulators in colistin resistance.Frontiers in microbiology · 2023Review
- The role of bacterial transport systems in the removal of host antimicrobial peptides in Gram-negative bacteria.FEMS microbiology reviews · 2022Review
- Risk Factors for the Development of Colistin Resistance during Colistin Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections.Microbiology spectrum · 2022Article
- Comparative analysis of the Colistin resistance-regulating gene cluster in Klebsiella species.Journal of microbiology (Seoul, Korea) · 2022Article
- Convergence of MCR-8.2 and Chromosome-Mediated Resistance to Colistin and Tigecycline in an NDM-5-Producing ST656Frontiers in cellular and infection microbiology · 2022Article
- A cyclic adenosine monophosphate response element-binding protein inhibitor enhances the antibacterial activity of polymyxin B by inhibiting the ATP hydrolyzation activity of CrrB.Frontiers in pharmacology · 2022Article
- Colistin Induces Resistance through Biofilm Formation, via IncreasedPathogens (Basel, Switzerland) · 2021Article
- A Resistance Mechanism in Non-Microbiology spectrum · 2021Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Colistin is one of the last-resort antibiotics used to treat carbapenem-resistant Klebsiella pneumoniae infection. Our previous studies indicated that clinical strains encoding CrrB with amino acid substitutions exhibited higher colistin resistance (MICs ≥512 mg/L) than did colistin-resistant strains encoding mutant MgrB, PmrB or PhoQ. Objectives: CrrAB may regulate another unknown mechanism(s) contributing to colistin resistance, besides modifications of LPS with 4-amino-4-deoxy-l-arabinose and phosphoethanolamine. Methods: To identify these potential unknown mechanism(s), a transposon mutant library of A4528 crrB(N141I) was constructed. Loci that might contribute to colistin resistance and were regulated by crrB were confirmed by deletion and complementation experiments. Results: Screening of 2976 transposon mutants identified 47 mutants in which the MICs of colistin were significantly decreased compared with that for the parent. Besides crrAB, crrC and pmrHFIJKLM operons, these 47 transposon insertion mutants included another 13 loci. Notably, transcript levels of one of these insertion targets, H239_3064 (encoding a putative RND-type efflux pump), were significantly increased in A4528 crrB(N141I) compared with the A4528 parent strain. Deletion of H239_3064 in the A4528 crrB(N141I) background resulted in an 8-fold decrease in the MIC of colistin; complementation of the deletion mutant with H239_3064 restored resistance to colistin. Susceptibilities of A4528-derived strains to other antibiotics were also tested. Mutations of crrB resulted in decreased susceptibility to tetracycline and tigecycline, and deletion of H239_3064 in A4528 crrB(N141I) attenuated this phenomenon. Conclusions: This study demonstrated that missense mutations of K. pneumoniae crrB lead to increased expression of H239_3064, leading in turn to decreased susceptibility to colistin, tetracycline and tigecycline.
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