ArticleAntimicrobial agents and chemotherapy2012
Temporal interplay between efflux pumps and target mutations in development of antibiotic resistance in Escherichia coli.
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 35 papers.
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Who cites it
35 citing papers in PubMed.
- A Comprehensive Review on Discovery, Development, the Chemistry of Quinolones, and Their Antimicrobial Resistance.Current topics in medicinal chemistry · 2026Review
- EPS inhibitor treatment of Salmonella impacts evolution without selecting for resistance to biofilm inhibition.NPJ biofilms and microbiomes · 2025Article
- Navigating fluoroquinolone resistance in Gram-negative bacteria: a comprehensive evaluation.JAC-antimicrobial resistance · 2024Review
- An insights into emerging trends to control the threats of antimicrobial resistance (AMR): an address to public health risks.Archives of microbiology · 2024Review
- Sodium Malonate Inhibits the AcrAB-TolC Multidrug Efflux Pump ofPathogens (Basel, Switzerland) · 2022Article
- Structural basis for inhibition of the drug efflux pump NorA from Staphylococcus aureus.Nature chemical biology · 2022Article
- The Evolution of Fluoroquinolone Resistance inInternational journal of molecular sciences · 2021Article
- Metal and Metal Oxide Nanoparticle as a Novel Antibiotic Carrier for the Direct Delivery of Antibiotics.International journal of molecular sciences · 2021Review
- Contribution of Different Mechanisms to Ciprofloxacin Resistance inFrontiers in microbiology · 2021Article
- Article
- Association between the rate of fluoroquinolones-resistant gram-negative bacteria and antibiotic consumption from China based on 145 tertiary hospitals data in 2014.BMC infectious diseases · 2020Article
- Overexpression of RamA, Which Regulates Production of the Multidrug Resistance Efflux Pump AcrAB-TolC, Increases Mutation Rate and Influences Drug Resistance Phenotype.Antimicrobial agents and chemotherapy · 2020Article
- Resistance and Virulence Mechanisms ofAntimicrobial agents and chemotherapy · 2019Article
- Chemical space of Escherichia coli dihydrofolate reductase inhibitors: New approaches for discovering novel drugs for old bugs.Medicinal research reviews · 2019Review
- Exposure to Sub-inhibitory Concentrations of the Chemosensitizer 1-(1-Naphthylmethyl)-Piperazine Creates Membrane Destabilization in Multi-Drug ResistantFrontiers in microbiology · 2019Article
- The Role of AcrAB-TolC Efflux Pumps on Quinolone Resistance of E. coli ST131.Current microbiology · 2018Article
- Chromosomal mutations that accompany qnr in clinical isolates of Escherichia coli.International journal of antimicrobial agents · 2018Article
- Epidemiology and characteristics of Escherichia coli sequence type 131 (ST131) from long-term care facility residents colonized intestinally with fluoroquinolone-resistant Escherichia coli.Diagnostic microbiology and infectious disease · 2017Article
- Development of Antibiotic Resistance during Simulated Treatment of Pseudomonas aeruginosa in Chemostats.PloS one · 2016Article
- Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 2.Antimicrobial agents and chemotherapy · 2015Review
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Authors and funding
7 authors.
Funding
Abstract
The emergence of resistance presents a debilitating change in the management of infectious diseases. Currently, the temporal relationship and interplay between various mechanisms of drug resistance are not well understood. A thorough understanding of the resistance development process is needed to facilitate rational design of countermeasure strategies. Using an in vitro hollow-fiber infection model that simulates human drug treatment, we examined the appearance of efflux pump (acrAB) overexpression and target topoisomerase gene (gyrA and parC) mutations over time in the emergence of quinolone resistance in Escherichia coli. Drug-resistant isolates recovered early (24 h) had 2- to 8-fold elevation in the MIC due to acrAB overexpression, but no point mutations were noted. In contrast, high-level (≥ 64× MIC) resistant isolates with target site mutations (gyrA S83L with or without parC E84K) were selected more readily after 120 h, and regression of acrAB overexpression was observed at 240 h. Using a similar dosing selection pressure, the emergence of levofloxacin resistance was delayed in a strain with acrAB deleted compared to the isogenic parent. The role of efflux pumps in bacterial resistance development may have been underappreciated. Our data revealed the interplay between two mechanisms of quinolone resistance and provided a new mechanistic framework in the development of high-level resistance. Early low-level levofloxacin resistance conferred by acrAB overexpression preceded and facilitated high-level resistance development mediated by target site mutation(s). If this interpretation is correct, then these findings represent a paradigm shift in the way quinolone resistance is thought to develop.
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