ArticleAntimicrobial agents and chemotherapy2012
Involvement of the AcrAB-TolC efflux pump in the resistance, fitness, and virulence of Enterobacter cloacae.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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77 citing papers in PubMed, 145 citations in OpenAlex.
- Impacts of feeding preweaned calves milk containing drug residues on the functional profile of the fecal microbiota.Scientific reports · 2018Trial
- Mutational analysis of multidrug efflux pump (AcrAB-TolC) in Enterobacter cloacae isolates from clinical samples.Scientific reports · 2026Article
- Role of the AmvAR efflux system on the pathogenesis of Acinetobacter baumannii.Scientific reports · 2026Article
- Antimicrobial Activity of Bioactive Peptides on Resistant Enterobacteriaceae and the Viability ofVeterinary sciences · 2026Article
- A novel GntR-ABC efflux system mediates oxidative stress response, drug resistance, motility and virulence inFrontiers in microbiology · 2026Article
- Efflux pump overexpression in fluoroquinolone multidrug resistance: molecular mechanisms, PK/PD implications, global epidemiology, and translational strategies.Frontiers in pharmacology · 2026Review
- Antimicrobial Peptides Against Antimicrobial-Resistant Bacteria: Focus on Machine Learning.Infection and drug resistance · 2026Review
- A review of research progress on periplasmic adaptor proteins in bacterial tripartite pumps.Frontiers in microbiology · 2026Review
- Beyond antibiotic resistance: evidence for resistance-nodulation-division (RND) efflux pumps as virulence determinants.Microbiology and molecular biology reviews : MMBR · 2025Review
- Review
- Positive Charge in an Antimalarial Compound Unlocks Broad-Spectrum Antibacterial Activity.JACS Au · 2025Article
- The AcrAB efflux pump contributes to the virulence of EnteroaggregativeFrontiers in cellular and infection microbiology · 2025Article
- Research progress on the role of microbiota in the pathogenesis of gallstone disease.Frontiers in microbiology · 2025Review
- Clinical characteristics, molecular epidemiology and mechanisms of colistin heteroresistance inFrontiers in cellular and infection microbiology · 2025Article
- Dual role ofiMetaOmics · 2024Article
- Potent synergy and sustained bactericidal activity of polymyxins combined with Gram-positive only class of antibiotics versus four Gram-negative bacteria.Annals of clinical microbiology and antimicrobials · 2024Article
- Molecular Mechanisms of Bacterial Resistance to Antimicrobial Peptides in the Modern Era: An Updated Review.Microorganisms · 2024Review
- Mode of the Interaction of Efflux Inhibitor Phenylalanyl-arginyl-β-naphtylamide with Bacterial Cells.Biomedicines · 2024Article
- Progress of Antimicrobial Mechanisms of Stilbenoids.Pharmaceutics · 2024Review
- A Multidrug-Resistant Extended-Spectrum Beta-Lactamase (ESBL)-Producing Enterobacter hormaechei Strain from Mixed Sprouts.Current microbiology · 2024Article
17 more citing papers are in PubMed but not listed here.
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9 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Multidrug efflux pumps have emerged as important mechanisms of antimicrobial resistance in bacterial pathogens. In order to cause infection, pathogenic bacteria require mechanisms to avoid the effects of host-produced compounds, and express efflux pumps may accomplish this task. In this study, we evaluated the effect of the inactivation of AcrAB-TolC on antimicrobial resistance, fitness, and virulence in Enterobacter cloacae, an opportunistic pathogen usually involved in nosocomial infections. Two different clinical isolates of E. cloacae were used, EcDC64 (multidrug resistance overexpressing the AcrAB-TolC efflux pump) and Jc194 (basal AcrAB-TolC expression). The acrA and tolC genes were deleted in strains EcDC64 and Jc194 to produce, respectively, EcΔacrA and EcΔtolC and JcΔacrA and JcΔtolC knockout (KO) derivatives. Antibiotic susceptibility testing was performed with all isolates, and we discovered that these mechanisms are involved in the resistance of E. cloacae to several antibiotics. Competition experiments were also performed with wild-type and isogenic KO strains. The competition index (CI), defined as the mutant/wild-type ratio, revealed that the acrA and tolC genes both affect the fitness of E. cloacae, as fitness was clearly reduced in the acrA and tolC KO strains. The median CI values obtained in vitro and in vivo were, respectively, 0.42 and 0.3 for EcDC64/EcΔacrA, 0.24 and 0.38 for EcDC64/EcΔtolC, 0.15 and 0.11 for Jc194/JcΔacrA, and 0.38 and 0.39 for Jc194/JcΔtolC. Use of an intraperitoneal mouse model of systemic infection revealed reduced virulence in both E. cloacae clinical strains when either the acrA or tolC gene was inactivated. In conclusion, the structural components of the AcrAB-TolC efflux pump appear to play a role in antibiotic resistance as well as environmental adaptation and host virulence in clinical isolates of E. cloacae.
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