ArticleThe Journal of antimicrobial chemotherapy2021
Resistance/fitness trade-off is a barrier to the evolution of MarR inactivation mutants in Escherichia coli.
Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
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- Bacteria can compensate the fitness costs of amplified resistance genes via a bypass mechanism.Nature communications · 2024Article
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- How selection shapes the short- and long-term dynamics of molecular evolution.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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- Epistasis decreases with increasing antibiotic pressure but not temperature.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- The fitness cost of horizontally transferred and mutational antimicrobial resistance inFrontiers in microbiology · 2023Review
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- The Atypical Antipsychotic Quetiapine Promotes Multiple Antibiotic Resistance in Escherichia coli.Journal of bacteriology · 2022Article
- Persistence of plasmid andFrontiers in microbiology · 2022Article
- Large-Scale Analysis of Fitness Cost ofFrontiers in cellular and infection microbiology · 2022Article
- Expression of the qepA1 gene is induced under antibiotic exposure.The Journal of antimicrobial chemotherapy · 2021Article
- Mutant RNA polymerase can reduce susceptibility to antibiotics via ppGpp-independent induction of a stringent-like response.The Journal of antimicrobial chemotherapy · 2021Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMutations that inactivate MarR reduce susceptibility to ciprofloxacin and competitive growth fitness in Escherichia coli. Both phenotypes are caused by overexpression of the MarA regulon, which includes the AcrAB-TolC drug efflux pump.
objectivesWe asked whether compensatory evolution could reduce the fitness cost of MarR-inactivating mutations without affecting resistance to ciprofloxacin.
methodsThe cost of overexpressing the AcrAB-TolC efflux pump was measured independently of MarA overexpression. Experimental evolution of MarR-inactive strains was used to select mutants with increased fitness. The acquired mutations were identified and their effects on drug susceptibility were measured.
resultsOverexpression of the AcrAB-TolC efflux pump was found not to contribute to the fitness cost of MarA regulon overexpression. Fitness-compensatory mutations were selected in marA and lon. The mutations reduced the level of MarA protein thus reducing expression of the MarA regulon. They restored growth fitness but also reduced resistance to ciprofloxacin.
conclusionsThe fitness cost caused by overexpression of the MarA regulon has multiple contributing factors. Experimental evolution did not identify any single pump-independent cost factor. Instead, efficient fitness compensation occurred only by mechanisms that reduce MarA concentration, which simultaneously reduce the drug resistance phenotype. This resistance/fitness trade-off is a barrier to the successful spread of MarR inactivation mutations in clinical isolates where growth fitness is essential.
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