Raising the alarm: fosfomycin resistance associated with non-susceptible inner colonies imparts no fitness cost to the primary bacterial uropathogen

Antimicrob Agents Chemother. 2024 Jan 10;68(1):e0080323. doi: 10.1128/aac.00803-23. Epub 2023 Dec 11.

Abstract

While fosfomycin resistance is rare, the observation of non-susceptible subpopulations among clinical Escherichia coli isolates is a common phenomenon during antimicrobial susceptibility testing (AST) in American and European clinical labs. Previous evidence suggests that mutations eliciting this phenotype are of high biological cost to the pathogen during infection, leading to current recommendations of neglecting non-susceptible colonies during AST. Here, we report that the most common route to fosfomycin resistance, as well as novel routes described in this work, does not impair virulence in uropathogenic E. coli, the major cause of urinary tract infections, suggesting a re-evaluation of current susceptibility guidelines is warranted.

Keywords: UPEC; antibiotic resistance; fosfomycin; glycolysis; urinary tract infection.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Escherichia coli Infections* / drug therapy
  • Escherichia coli Infections* / microbiology
  • Fosfomycin* / pharmacology
  • Humans
  • Urinary Tract Infections* / drug therapy
  • Urinary Tract Infections* / microbiology
  • Uropathogenic Escherichia coli* / genetics

Substances

  • Fosfomycin
  • Anti-Bacterial Agents