ArticleAntimicrobial agents and chemotherapy2005
Biological cost of single and multiple norfloxacin resistance mutations in Escherichia coli implicated in urinary tract infections.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- Plasmid-mediated quinolone resistance in Enterobacteriaceae: a systematic review with a focus on Mediterranean countries.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2017Pooled it
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- Mutation- and Transcription-Driven Omic Burden of Daptomycin/Dalbavancin-R and Glycopeptide-RS Fitness Costs in High-Risk MRSA: A Nexus in Antimicrobial Resistance Mechanisms-Genome Proneness-Compensatory Adaptations.Antibiotics (Basel, Switzerland) · 2025Article
- Fitness Burden for the Stepwise Acquisition of First- and Second-Line Antimicrobial Reduced-Susceptibility in High-Risk ESKAPE MRSA Superbugs.Antibiotics (Basel, Switzerland) · 2025Article
- The fitness connection of antibiotic resistance.Frontiers in microbiology · 2025Article
- Assessing the Influence of Urine pH on the Efficacy of Ciprofloxacin and Fosfomycin in Immunocompetent and Immunocompromised Murine Models ofAntibiotics (Basel, Switzerland) · 2024Article
- Effects of pH on the Pathogenicity ofInternational journal of molecular sciences · 2024Article
- Acidic Urine pH and Clinical Outcome of Lower Urinary Tract Infection in Kidney Transplant Recipients Treated with Ciprofloxacin and Fosfomycin.Antibiotics (Basel, Switzerland) · 2024Article
- Chance Favors the Prepared Genomes: Horizontal Transfer Shapes the Emergence of Antibiotic Resistance Mutations in Core Genes.Molecular biology and evolution · 2023Article
- Commensal Fitness Advantage May Contribute to the Global Dissemination of Multidrug-Resistant Lineages of Bacteria-The Case of UropathogenicPathogens (Basel, Switzerland) · 2023Article
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- Mechanisms of antibiotic action shape the fitness landscapes of resistance mutations.Computational and structural biotechnology journal · 2022Article
- Mutational Diversity in the Quinolone Resistance-Determining Regions of Type-II Topoisomerases ofAntibiotics (Basel, Switzerland) · 2021Review
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- Limited Multidrug Resistance Efflux Pump Overexpression among Multidrug-Resistant Escherichia coli Strains of ST131.Antimicrobial agents and chemotherapy · 2021Article
- Predicting antimicrobial resistance using conserved genes.PLoS computational biology · 2020Article
- Development and selection of low-level multi-drug resistance over an extended range of sub-inhibitory ciprofloxacin concentrations in Escherichia coli.Scientific reports · 2020Article
- Resistance and Virulence Mechanisms ofAntimicrobial agents and chemotherapy · 2019Article
- Article
- Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to fluoroquinolones in urinary tract infection (UTIs) caused by Escherichia coli is associated with multiple mutations, typically those that alter DNA gyrase and DNA topoisomerase IV and those that regulate AcrAB-TolC-mediated efflux. We asked whether a fitness cost is associated with the accumulation of these multiple mutations. Mutants of the susceptible E. coli UTI isolate Nu14 were selected through three to five successive steps with norfloxacin. Each selection was performed with the MIC of the selected strain. After each selection the MIC was measured; and the regions of gyrA, gyrB, parC, and parE, previously associated with resistance mutations, and all of marOR and acrR were sequenced. The first selection step yielded mutations in gyrA, gyrB, and marOR. Subsequent selection steps yielded mutations in gyrA, parE, and marOR but not in gyrB, parC, or acrR. Resistance-associated mutations were identified in almost all isolates after selection steps 1 and 2 but in less than 50% of isolates after subsequent selection steps. Selected strains were competed in vitro, in urine, and in a mouse UTI infection model against the starting strain, Nu14. First-step mutations were not associated with significant fitness costs. However, the accumulation of three or more resistance-associated mutations was usually associated with a large reduction in biological fitness, both in vitro and in vivo. Interestingly, in some lineages a partial restoration of fitness was associated with the accumulation of additional mutations in late selection steps. We suggest that the relative biological costs of multiple mutations may influence the evolution of E. coli strains that develop resistance to fluoroquinolones.
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