Beta-lactamase; Penicillin-binding protein (Beta-lactamase (BL); Penicillin-binding protein (PBP))

Beta-lactamases are enzymes (EC 3.5.2.6) produced by bacteria that provide resistance by hydrolyzing the β-lactam ring of penicillins and related antibiotics, rendering them ineffective[2][6]. Their rapid evolution and gene transfer among bacteria have made them major contributors to antibiotic resistance globally. Penicillin-binding proteins (PBPs) are bacterial enzymes involved in cell wall biosynthesis, particularly cross-linking peptidoglycan strands and regulating wall structure[5][4][6]. PBPs are the intended targets of β-lactam antibiotics; binding of these drugs to PBPs inhibits their transpeptidase activity, thereby weakening the cell wall and leading to bacterial death. Mutations leading to low-affinity PBPs (e.g., PBP2a in MRSA) or overproduction of β-lactamases are prominent mechanisms of acquired resistance[4][5][6]. Both PBPs and β-lactamases share structural similarity, evolutionary relationships, and a serine-containing active site in many cases[6].

Other names

Beta-lactamasePBPPenicillinaseAmpC β-lactamaseDD-transpeptidase

Beta-lactamase inhibitors bind and irreversibly inactivate β-lactamase enzymes, restoring efficacy of β-lactam antibiotics. Beta-lactam antibiotics covalently bind to PBPs, preventing cross-linking of peptidoglycan and leading to cell lysis.