FosA3 emerging in clinical carbapenemase-producing C. freundii

Front Cell Infect Microbiol. 2024 Aug 6:14:1447933. doi: 10.3389/fcimb.2024.1447933. eCollection 2024.

Abstract

Fosfomycin (FOS) is an effective antibiotic against multidrug-resistant Enterobacterales, but its effectiveness is reducing. Little is known on the current prevalence of FosA enzymes in low-risk pathogens, such as Citrobacter freundii. The aim of the study was the molecular characterization of a carbapenemase- and FosA-producing C. freundii collected in Italy. AK867, collected in 2023, showed an XDR profile, retaining susceptibility only to colistin. AK867 showed a FOS MIC >128 mg/L by ADM. Based on WGS, AK867 belonged to ST116 and owned a wide resistome, including fosA3, blaKPC-2, and blaVIM-1. fosA3 was carried by a conjugative pKPC-CAV1312 plasmid of 320,480 bp, on a novel composite transposon (12,907 bp). FosA3 transposon shared similarities with other fosA3-harboring pKPC-CAV1312 plasmids among Citrobacter spp. We report the first case of FosA3 production in clinical carbapenemase-producing C. freundii ST116. The incidence of FosA3 enzymes is increasing among Enterobacterales, affecting even low-virulence pathogens, as C. freundii.

Keywords: Citrobacter freundii; carbapenemases; fosA3 gene; fosfomycin; fosfomycin resistance.

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Citrobacter freundii* / drug effects
  • Citrobacter freundii* / enzymology
  • Citrobacter freundii* / genetics
  • DNA Transposable Elements
  • Drug Resistance, Multiple, Bacterial / genetics
  • Enterobacteriaceae Infections* / microbiology
  • Fosfomycin* / pharmacology
  • Humans
  • Italy / epidemiology
  • Microbial Sensitivity Tests
  • Plasmids / genetics
  • Whole Genome Sequencing
  • beta-Lactamases* / genetics
  • beta-Lactamases* / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • beta-Lactamases
  • carbapenemase
  • DNA Transposable Elements
  • Fosfomycin

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was supported by the research project grant NU23J-09-00067 provided by the Czech Health Research Council and by the project National Institute of Virology and Bacteriology (Programme EXCELES, ID Project No. LX22NPO5103)—funded by the European Union—Next Generation EU and by the EU funding within the NextGenerationEU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT).