Increased mutability to fosfomycin resistance in Proteus mirabilis clinical isolates

Infect Genet Evol. 2018 Mar:58:27-33. doi: 10.1016/j.meegid.2017.12.012. Epub 2017 Dec 15.

Abstract

In the present study, we screened a collection of 77 Proteus mirabilis clinical isolates for the presence of mutators, using the frequency of both rifampicin and fosfomycin resistance mutants as markers of spontaneous mutagenesis. We found that none of the strains in our collection are mutators for the rifampicin resistance (RifR) marker. Nevertheless, a significant fraction of the isolates (17%) show high frequencies of fosfomycin resistant mutants (FosR). We show that this increased mutability to FosR correlates with a low level of resistance to Fosfomycin (MICs 8-64μg/ml). These strains also show high frequencies of single step mutants with clinically relevant FosR resistance levels (MIC ≥256μg/ml). Our findings point out to the risk of fosfomycin resistance emergence in P. mirabilis.

Keywords: Fosfomycin resistance; Mutagenesis; Mutators; Proteus mirabilis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Drug Resistance, Bacterial*
  • Fosfomycin / pharmacology*
  • Fosfomycin / therapeutic use
  • Humans
  • Microbial Sensitivity Tests
  • Mutation Rate
  • Mutation*
  • Proteus Infections / drug therapy
  • Proteus Infections / microbiology*
  • Proteus mirabilis / drug effects*
  • Proteus mirabilis / genetics*

Substances

  • Anti-Bacterial Agents
  • Fosfomycin