ArticleEBioMedicine2019
Quantitative contribution of efflux to multi-drug resistance of clinical Escherichia coli and Pseudomonas aeruginosa strains.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 52 citations in OpenAlex.
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- Targeted isolation of TolC-dependent phages reveals dual strategies for combating multidrug-resistant avianFrontiers in microbiology · 2026Article
- Molecular insights into the inhibition of MexCD-OprJ efflux pumps by menthol and thymol in Pseudomonas aeruginosa.Antonie van Leeuwenhoek · 2025Article
- A pH-sensitive motif in an outer membrane protein activates bacterial membrane vesicle production.Nature communications · 2024Article
- Rapid detection ofFrontiers in microbiology · 2024Article
- Comparative Genetic Characterization of CTX-M-ProducingMicroorganisms · 2023Article
- Genetic components ofFrontiers in microbiology · 2023Article
- Biofilms and efflux pump regulatory gene (Veterinary world · 2022Article
- Advanced transcriptomic analysis reveals the role of efflux pumps and media composition in antibiotic responses of Pseudomonas aeruginosa.Nucleic acids research · 2022Article
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- Association of multidrug resistance behavior of clinical Pseudomonas aeruginosa to pigment coloration.European journal of medical research · 2022Article
- Evolutionary Dynamics between Phages and Bacteria as a Possible Approach for Designing Effective Phage Therapies against Antibiotic-Resistant Bacteria.Antibiotics (Basel, Switzerland) · 2022Review
- Identification of the target and mode of action for the prokaryotic nucleotide excision repair inhibitor ATBC.Bioscience reports · 2022Article
- Molecular rationale for the impairment of the MexAB-OprM efflux pump by a single mutation in MexA.Computational and structural biotechnology journal · 2022Article
- Differentially Expressed Genes ofInfection and drug resistance · 2022Article
- Outer membrane permeability: Antimicrobials and diverse nutrients bypass porins inProceedings of the National Academy of Sciences of the United States of America · 2021Article
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- Exploring the Contribution of the AcrB Homolog MdtF to Drug Resistance and Dye Efflux in a Multidrug ResistantAntibiotics (Basel, Switzerland) · 2021Article
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Authors and funding
14 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundEfflux pumps mediate antimicrobial resistance in several WHO critical priority bacterial pathogens. However, most available data come from laboratory strains. The quantitative relevance of efflux in more relevant clinical isolates remains largely unknown.
methodsWe developed a versatile method for genetic engineering in multi-drug resistant (MDR) bacteria, and used this method to delete tolC and specific antibiotic-resistance genes in 18 representative MDR clinical E. coli isolates. We determined efflux activity and minimal inhibitory concentrations for a diverse set of clinically relevant antibiotics in these mutants. We also deleted oprM in MDR P. aeruginosa strains and determined the impact on antibiotic susceptibility.
findingstolC deletion abolished detectable efflux activity in 15 out of 18 tested E. coli strains, and modulated antibiotic susceptibility in many strains. However, all mutant strains retained MDR status, primarily because of other, antibiotic-specific resistance genes. Deletion of oprM altered antibiotic susceptibility in a fraction of clinical P. aeruginosa isolates.
interpretationEfflux modulates antibiotic resistance in clinical MDR isolates of E. coli and P. aeruginosa. However, when other antimicrobial-resistance mechanisms are present, inhibition of MDR efflux pumps alone is often not sufficient to restore full susceptibility even for antibiotics with a dramatic impact of efflux in laboratory strains. We propose that development of novel antibiotics should include target validation in clinical MDR isolates. FUND: Innovative Medicines Initiative of European Union and EFPIA, Schweizerischer Nationalfonds, Swiss National Research Program 72, EU Marie Skłodowska-Curie program. The funders played no role in design, data collection, data analysis, interpretation, writing of the report, and in the decision to submit the paper for publication.
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