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Increased mutability to fosfomycin resistance in Proteus mirabilis clinical isolates

Marina R B Fonseca1, Juliana L Sato1, Marco A Lima-Noronha1

  • 1Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
|December 18, 2017
PubMed

Insights

A study found that 17% of Proteus mirabilis clinical isolates exhibit high mutation rates for fosfomycin resistance. This suggests a significant risk for the emergence of fosfomycin resistance in P. mirabilis infections.

Area of Science:

  • Microbiology
  • Antimicrobial Resistance
  • Clinical Infectious Diseases

Background:

  • Proteus mirabilis is a common cause of urinary tract infections.
  • Antimicrobial resistance is a growing global health concern.
  • Fosfomycin is an important antibiotic for treating multidrug-resistant Gram-negative infections.

Purpose of the Study:

  • To screen clinical isolates of Proteus mirabilis for mutator phenotypes.
  • To assess the frequency of spontaneous mutations conferring resistance to rifampicin and fosfomycin.
  • To evaluate the risk of fosfomycin resistance emergence in P. mirabilis.

Main Methods:

  • Screening of 77 Proteus mirabilis clinical isolates.
  • Utilizing rifampicin resistance (RifR) and fosfomycin resistance (FosR) mutant frequencies as markers for spontaneous mutagenesis.
  • Determining minimum inhibitory concentrations (MICs) for fosfomycin resistance.

Main Results:

  • No isolates showed mutator phenotypes for rifampicin resistance.
  • 17% of isolates exhibited high frequencies of fosfomycin resistant mutants (FosR).
  • Increased FosR mutability correlated with low-level fosfomycin resistance (MICs 8-64 μg/ml) and high frequencies of single-step mutants with clinically relevant resistance (MIC ≥256 μg/ml).

Conclusions:

  • A notable fraction of P. mirabilis clinical isolates possess an elevated mutation rate towards fosfomycin resistance.
  • These findings highlight a potential risk for the rapid emergence of clinically significant fosfomycin resistance in P. mirabilis.
  • Further surveillance and understanding of resistance mechanisms are warranted.
Keywords:
Fosfomycin resistanceMutagenesisMutatorsProteus mirabilis

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