Discovery of amino acid substitutions in penicillin-binding proteins associated with adaptation to D-Ala-D-Lac in vancomycin-resistant <i>Enterococcus faecalis</i>.

ABSTRACT: The bacterial cell wall, essential for structural integrity, is synthesized with penicillin-binding proteins (PBPs). Vancomycin-resistant enterococci (VRE) evades vancomycin by replacing D-Ala-D-Ala in their cell wall precursors with D-Ala-D-Lac, reducing the drug's effectiveness. However, how PBPs-which typically use D-Ala-D-Ala as a substrate-adapt to recognize D-Ala-D-Lac remains unclear. Here, we performed Sanger sequencing and alignment of PBP genes from both vancomycin-susceptible and -resistant E. faecalis strains to identify mutations, following amplification by PCR. We then applied homology modeling to assess structural impacts of these changes on PBPs and conducted docking studies to investigate ligand-binding interactions. For the first time, we identified specific adapta

SUBMITTER: Caglayan N 

PROVIDER: S-EPMC11850342 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature