ArticleThe Journal of antimicrobial chemotherapy2017
Fitness cost constrains the spectrum of marR mutations in ciprofloxacin-resistant Escherichia coli.
Article in The Journal of antimicrobial chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed.
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- Diversity of Transcriptional Regulatory Adaptation in E. coli.Molecular biology and evolution · 2024Article
- The induced and intrinsic resistance ofMicrobiology spectrum · 2024Article
- Clonal and resistance profiles of fluoroquinolone-resistant uropathogenicFrontiers in microbiology · 2024Article
- QUIRMIA-A Phenotype-Based Algorithm for the Inference of Quinolone Resistance Mechanisms inAntibiotics (Basel, Switzerland) · 2023Article
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- The Atypical Antipsychotic Quetiapine Promotes Multiple Antibiotic Resistance in Escherichia coli.Journal of bacteriology · 2022Article
- The role of chemotaxis and efflux pumps on nitrate reduction in the toxic regions of a ciprofloxacin concentration gradient.The ISME journal · 2021Article
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- Expression of the qepA1 gene is induced under antibiotic exposure.The Journal of antimicrobial chemotherapy · 2021Article
- Metabolic fitness landscapes predict the evolution of antibiotic resistance.Nature ecology & evolution · 2021Article
- Balancing Positive and Negative Selection:mBio · 2021Article
- Limited Multidrug Resistance Efflux Pump Overexpression among Multidrug-Resistant Escherichia coli Strains of ST131.Antimicrobial agents and 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
- Diffusible Signaling Factor, a Quorum-Sensing Molecule, Interferes with and Is Toxic Towards Bdellovibrio bacteriovorus 109J.Microbial ecology · 2021Article
- Genome-Based Analyses of Fitness Effects and Compensatory Changes Associated with Acquisition ofAntibiotics (Basel, Switzerland) · 2021Article
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4 authors.
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Abstract
objectivesTo determine whether the spectrum of mutations in marR in ciprofloxacin-resistant clinical isolates of Escherichia coli shows evidence of selection bias, either to reduce fitness costs, or to increase drug resistance. MarR is a repressor protein that regulates, via MarA, expression of the Mar regulon, including the multidrug efflux pump AcrAB-TolC.
methodsIsogenic strains carrying 36 different marR alleles identified in resistant clinical isolates, or selected for resistance in vitro, were constructed. Drug susceptibility and relative fitness in growth competition assays were measured for all strains. The expression level of marA, and of various efflux pump components, as a function of specific mutations in marR, was measured by qPCR.
resultsThe spectrum of genetic alterations in marR in clinical isolates is strongly biased against inactivating mutations. In general, the alleles found in clinical isolates conferred a lower level of resistance and imposed a lower growth fitness cost than mutations selected in vitro. The level of expression of MarA correlated well with the MIC of ciprofloxacin. This supports the functional connection between mutations in marR and reduced susceptibility to ciprofloxacin.
conclusionsMutations in marR selected in ciprofloxacin-resistant clinical isolates are strongly biased against inactivating mutations. Selection favours mutant alleles that have the lowest fitness costs, even though these cause only modest reductions in drug susceptibility. This suggests that selection for high relative fitness is more important than selection for increased resistance in determining which alleles of marR will be selected in resistant clinical isolates.
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