Penicillin-binding proteins (PBPs) (PBPs)

Penicillin-binding proteins (PBPs) in Enterococcus faecalis are a family of membrane-bound enzymes essential for the biosynthesis and maintenance of the bacterial peptidoglycan layer [2, 9]. These proteins are categorized into Class A (bifunctional transglycosylases/transpeptidases), Class B (monofunctional transpeptidases), and Class C (carboxypeptidases), each playing a distinct role in cell wall cross-linking and morphogenesis [1, 2]. In E. faecalis, PBP4 is the primary low-affinity transpeptidase responsible for the organism's intrinsic resistance to most cephalosporins and its reduced susceptibility to other beta-lactams [2, 5]. PBPs serve as the molecular targets for beta-lactam antibiotics, which inhibit the transpeptidation reaction by acylating the enzyme's active site [6, 7]. Mutations or overproduction of specific PBPs, particularly PBP4, are major drivers of clinical resistance, complicating the treatment of serious infections such as endocarditis and bacteremia [5, 8]. Consequently, these proteins are central to the study of antibiotic resistance mechanisms and the development of synergistic drug combinations [12].

Other names

Penicillin-binding protein 4 (PBP4)Penicillin-binding protein 5 (PBP5)PBP1a (PonA)PBP1b (PbpF)PBP1c (PbpZ)PBP2 (PbpA)PBP3 (PbpB)D,D-carboxypeptidase (DacA)

Beta-lactam antibiotics function as structural analogs of the D-alanyl-D-alanine terminus of peptidoglycan precursors. They covalently bind to the active-site serine residue within the transpeptidase domain of PBPs, forming a stable acyl-enzyme complex [2, 7]. This irreversible inhibition prevents the cross-linking of peptidoglycan chains, compromising the structural integrity of the bacterial cell wall and ultimately leading to cell lysis or growth arrest [6, 9].