Genetic analysis of faropenem-resistant Enterococcus faecalis in urinary isolates

Noriyuki Hiraga1, Tetsuro Muratani, Seiji Naito

  • 1Department of Urology, Graduate School of Medical Sciences, Kyushu University, Japan.

Insights

Faropenem resistance in Enterococcus faecalis is not due to beta-lactamase or PBP overproduction. Resistance develops from mutations in penicillin-binding protein 4 (PBP4), decreasing its affinity for faropenem.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Enterococcus faecalis is a common cause of urinary tract infections.
  • Penicillin resistance in E. faecalis can arise through various mechanisms.
  • Understanding faropenem resistance is crucial for effective treatment.

Purpose of the Study:

  • Investigate the mechanisms of faropenem resistance in E. faecalis isolates.
  • Determine the role of beta-lactamase production, PBP overproduction, and PBP mutations in resistance.
  • Characterize the specific mutations in PBP4 associated with faropenem resistance.

Main Methods:

  • Isolation of faropenem-resistant E. faecalis from urine specimens.
  • Testing for beta-lactamase production and PBP overproduction.
  • Sequencing of the pbp4 gene to identify mutations.
  • Assessing the affinity of faropenem for PBP4.

Main Results:

  • No beta-lactamase production or PBP overproduction was observed in resistant isolates.
  • Decreased affinities of faropenem for PBP4 were detected in resistant strains.
  • Single amino acid substitutions (positions 475, 520, or 605) or double substitutions (positions 520 and 605) in PBP4 were identified.

Conclusions:

  • Faropenem resistance in E. faecalis is primarily mediated by reduced affinity of PBP4.
  • Point mutations in the pbp4 gene lead to these affinity changes.
  • These findings highlight the importance of PBP4 mutations in the development of carbapenem resistance in E. faecalis.

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