Penicillin-binding proteins 1–4 (Staphylococcus aureus) (PBPs 1–4)

Penicillin-binding proteins (PBPs) 1–4 are essential membrane-bound enzymes in Staphylococcus aureus that facilitate the assembly and maintenance of the bacterial cell wall [Sauvage et al., 2008]. These proteins, categorized as PBP1, PBP2, PBP3, and PBP4, are responsible for the transpeptidation and, in the case of PBP2, transglycosylation reactions required to cross-link peptidoglycan layers [Pinho et al., 2001]. This cross-linking provides the mechanical strength necessary for the bacterium to survive high internal osmotic pressure [Memmi et al., 2008]. PBPs are the definitive targets for the beta-lactam class of antibiotics, which mimic the natural substrate of the enzymes to form a stable, inactive covalent complex [StatPearls, 2023]. Inhibition of these enzymes halts cell wall synthesis, triggers autolytic enzymes, and results in bacterial cell death [PubMed: PMC3531343]. While PBPs 1–4 are native to all S. aureus strains, their clinical relevance is often discussed alongside resistance mechanisms like the acquisition of PBP2a, which allows the bacteria to maintain cell wall synthesis even in the presence of most beta-lactams [UniProt, 2024].

Other names

Penicillin-binding protein 1Penicillin-binding protein 2Penicillin-binding protein 3Penicillin-binding protein 4PBP1PBP2PBP3PBP4DD-transpeptidasePeptidoglycan glycosyltransferase

Beta-lactam antibiotics act as structural analogs of the D-alanyl-D-alanine terminus of peptidoglycan precursors, covalently binding to the active site serine of PBPs to irreversibly inhibit their transpeptidase activity, thereby preventing cell wall cross-linking and leading to bacterial lysis [StatPearls, 2023].