Penicillin-binding protein 5 sequence alterations in clinical isolates of Enterococcus faecium with different levels

T Rybkine1, J L Mainardi, W Sougakoff

  • 1L.R.M.A. UFR Broussais-Hôtel-Dieu et UFR Pitié-Salpétrière, Université Paris VI, France.

Insights

Penicillin-binding protein 5 (PBP 5) mutations drive beta-lactam antibiotic resistance in Enterococcus faecium. Specific amino acid changes in PBP 5 correlate with high-level resistance, impacting treatment options.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antibiotic Resistance

Background:

  • Penicillin-binding protein (PBP) 5 is a primary target for beta-lactam antibiotics in Enterococcus faecium.
  • PBP 5 plays a crucial role in mediating resistance to beta-lactam antibiotics within this bacterial species.

Purpose of the Study:

  • To analyze PBP 5 variants in clinical Enterococcus faecium isolates with varying beta-lactam resistance levels.
  • To identify specific amino acid substitutions in PBP 5 associated with high-level beta-lactam resistance.

Main Methods:

  • Analysis of PBP 5 variants from 15 clinical Enterococcus faecium isolates.
  • Correlation of specific amino acid substitutions with observed minimum inhibitory concentrations (MICs) for beta-lactam antibiotics.

Main Results:

  • Highly beta-lactam-resistant isolates predominantly produced low-affinity PBP 5 in small quantities.
  • Key amino acid substitutions identified include Ala/Ile for Thr-499, Glu for Val-629, and Pro for Ser-667.
  • Specific mutations near the SDN box (Met-485 to Thr/Ala) and insertions near Ser-466 were linked to high ampicillin MICs (up to 256 µg/mL).

Conclusions:

  • Specific point mutations and their combinations within PBP 5 are key determinants of high-level beta-lactam resistance in Enterococcus faecium.
  • Understanding these mutations can inform strategies to combat antibiotic resistance in E. faecium infections.

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