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Published on: July 3, 2016
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.
Abstract:
The low-affinity penicillin-binding protein (PBP) 5 is the main beta-lactam target and is responsible for resistance to this class of antibiotics in Enterococcus faecium. The PBP 5 variants of 15 clinical isolates (including 8 resistant to vancomycin) with different levels of beta-lactam resistance were analyzed. Most of the highly beta-lactam-resistant isolates produced small quantities of PBP 5 of low affinity. This was associated with particular amino acid substitutions: an Ala or Ile for Thr-499, a Glu for Val-629, and a Pro for Ser-667. A change of Met-485 to Thr or Ala (adjacent to the conserved SDN box) was observed in isolates with MICs of ampicillin of 64 or 128 microg/mL, respectively. In the 2 most resistant isolates, with MICs of ampicillin of 256 microg/mL, an additional Ser was present just after Ser-466. Thus, particular point mutations in PBP 5 and combinations thereof may lead to high-level beta-lactam resistance in E. faecium.
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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