ArticleResearch in microbiology
Analysis of AcrB in Klebsiella pneumoniae reveals natural variants promoting enhanced multidrug resistance.
Article in Research in microbiology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Genetic variants of AcrAB and OqxAB and the impact of efflux pump inhibition on ciprofloxacin and amikacin resistance in clinical isolates of Klebsiella pneumoniae from Lima, Peru.BMC microbiology · 2026Article
- Evaluation of a machine learning system for genomic antimicrobial susceptibility determination on a clinically representative test set.Microbiology spectrum · 2026Article
- Conformational plasticity across phylogenetic clusters of RND multidrug efflux pumps and its impact on substrate specificity.Nature communications · 2025Article
- Domestic laundering of healthcare textiles: Disinfection efficacy and risks of antibiotic resistance transmission.PloS one · 2025Article
- Article
- Antibiotic Resistance in the Elderly: Mechanisms, Risk Factors, and Solutions.Microorganisms · 2024Review
- Structural and functional diversity of Resistance-Nodulation-Division (RND) efflux pump transporters with implications for antimicrobial resistance.Microbiology and molecular biology reviews : MMBR · 2024Review
- Navigating fluoroquinolone resistance in Gram-negative bacteria: a comprehensive evaluation.JAC-antimicrobial resistance · 2024Review
- Relevance of the Adjuvant Effect between Cellular Homeostasis and Resistance to Antibiotics in Gram-Negative Bacteria with Pathogenic Capacity: A Study ofAntibiotics (Basel, Switzerland) · 2024Review
- Identification of the Major Facilitator Superfamily Efflux Pump KpsrMFS inInternational journal of molecular sciences · 2024Article
- Article
- Functionally distinct mutations within AcrB underpin antibiotic resistance in different lifestyles.npj antimicrobials and resistance · 2023Article
- Unveiling the genome of a high-risk pandrug-resistant Klebsiella pneumoniae emerging in the Brazilian Amazon Region, 2022.Memorias do Instituto Oswaldo Cruz · 2023Article
- Discovering interrelated natural mutations of efflux pump KmrA from Klebsiella pneumoniae that confer increased multidrug resistance.Protein science : a publication of the Protein Society · 2022Article
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Authors and funding
3 authors.
Funding
Abstract
Infections caused by Klebsiella pneumoniae are often difficult to manage due to the high frequency of multidrug resistance, often conferred by efflux pumps. In this study, we analyzed sequence variations of the major RND family multidrug efflux pump AcrB from 387 assembled K. pneumoniae genomes. We confirm that AcrB is a highly-conserved efflux pump in K. pneumoniae, and identified several variants that were prevalent in clinical isolates. Molecular dynamics analyses on two of these variants (L118M and S966A) suggested conformational changes that may correlate with increased drug efflux capabilities. The L118M change resulted in enhanced protein rigidity while the flexibility of drug binding pockets was stable or increased, and the interactions between the proximal pockets and water molecules were stronger. For S966A, the significantly enlarged proximal pocket suggested higher drug accommodation ability. Consistent with these predictions, the L118M and S966A variants conferred a slightly increased ability to grow in the presence of tetracycline and to survive cefoxitin exposure when overexpressed. In summary, our results suggest that the emergence of enhanced-function AcrB variants may be a potential risk for increased antibiotic resistance in clinical K. pneumoniae isolates.
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