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FosA3 emerging in clinical carbapenemase-producing C. freundii

Vittoria Mattioni Marchetti1, Irene Venturelli2, Tiziana Cassetti2

  • 1Microbiology and Clinical Microbiology Unit, Scienze Clinico, Chirurgiche, Diagnostiche, Pediatriche (SCCDP) Department, University of Pavia, Pavia, Italy.

Frontiers in Cellular and Infection Microbiology
|September 9, 2024
PubMed

Insights

Fosfomycin resistance is rising in multidrug-resistant bacteria. Researchers identified the FosA3 enzyme in Citrobacter freundii, a low-risk pathogen, highlighting the need for ongoing surveillance of antibiotic resistance mechanisms.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Fosfomycin (FOS) is crucial against multidrug-resistant Enterobacterales, but its efficacy is declining.
  • The prevalence of FosA enzymes, particularly in lower-risk pathogens like Citrobacter freundii, remains understudied.

Purpose of the Study:

  • To perform molecular characterization of a carbapenemase- and FosA-producing Citrobacter freundii isolate from Italy.
  • To investigate the genetic basis of fosfomycin resistance in this clinical isolate.

Main Methods:

  • Whole Genome Sequencing (WGS) for genomic and resistome analysis.
  • Antimicrobial susceptibility testing, including Fosfomycin Minimum Inhibitory Concentration (MIC) determination.
  • Plasmid analysis and characterization of mobile genetic elements.

Main Results:

  • A 2023 isolate, AK867, exhibited an extensively drug-resistant (XDR) profile, susceptible only to colistin.
  • WGS revealed the isolate belonged to ST116 and harbored fosA3, blaKPC-2, and blaVIM-1 genes.
  • The fosA3 gene was located on a novel composite transposon within a conjugative pKPC-CAV1312 plasmid.

Conclusions:

  • This study reports the first instance of FosA3 production in a clinical carbapenemase-producing Citrobacter freundii ST116 isolate.
  • The increasing incidence of FosA3 enzymes in Enterobacterales, including low-virulence species like C. freundii, poses a growing threat to fosfomycin effectiveness.
Keywords:
Citrobacter freundiicarbapenemasesfosA3 genefosfomycinfosfomycin resistance

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