Enterococcus faecium PBP5-S/R, the missing link between PBP5-S and PBP5-R.

Area of Science:

• Microbiology
• Molecular Biology
• Evolutionary Biology

Background:

• Enterococcus faecium is a significant opportunistic pathogen.
• Ampicillin resistance in E. faecium is a growing clinical concern.
• Penicillin-binding protein 5 (PBP5) is a key determinant of beta-lactam resistance in E. faecium.

Purpose of the Study:

• To investigate the evolutionary pathways of ampicillin resistance in Enterococcus faecium.
• To characterize novel PBP5 sequences observed in E. faecium strains.
• To explore the relationship between PBP5 sequence variations and ampicillin minimum inhibitory concentrations (MICs).

Main Methods:

• Genomic sequencing of E. faecium strains.
• Analysis of PBP5 gene sequences.
• Determination of ampicillin MICs for characterized strains.

Main Results:

• A subset of E. faecium strains, particularly from subclade A2, exhibited hybrid PBP5 sequences (PBP5-S/R).
• These hybrid sequences represent an intermediate stage in the amino acid evolution from the susceptible (S) form to the resistant (R) form of PBP5.
• The observed amino acid substitutions in hybrid PBP5 sequences did not consistently correlate with ampicillin MICs.

Conclusions:

• Hybrid PBP5-S/R sequences represent a transitional evolutionary state in ampicillin resistance development in E. faecium.
• The evolution of ampicillin resistance is complex, involving intermediate PBP5 forms.
• Further research is needed to fully understand the impact of these intermediate PBP5 variants on antibiotic resistance mechanisms.