Serine beta-lactamase (Classes A, C, and D) (SBL) (SBL)

Serine beta-lactamases (SBLs) are a diverse group of bacterial enzymes that catalyze the hydrolysis of the beta-lactam ring, the core structural component of antibiotics such as penicillins, cephalosporins, and carbapenems (Bush & Jacoby, 2010). These enzymes are classified under the Ambler system into Classes A, C, and D, all of which utilize a conserved serine residue in their active site to initiate a nucleophilic attack on the antibiotic (Ambler, 1980). Class A includes common resistance factors like TEM-1 and the carbapenemase KPC; Class C includes AmpC enzymes; and Class D consists of OXA-type enzymes often associated with carbapenem resistance in Acinetobacter species (Drawz & Bonomo, 2010). By neutralizing the antibiotic before it can reach its target penicillin-binding proteins, SBLs serve as a primary defense mechanism for both Gram-positive and Gram-negative pathogens. Therapeutic strategies often involve combining a beta-lactam antibiotic with a beta-lactamase inhibitor, such as clavulanic acid or avibactam, to protect the antibiotic from degradation and restore its efficacy (StatPearls, 2023). The continuous evolution and global spread of these enzymes, particularly extended-spectrum beta-lactamases (ESBLs), represent a major threat to modern medicine.

Other names

Beta-lactamaseAmbler Class A/C/D beta-lactamasePenicillinaseCephalosporinaseCarbapenemaseSerine hydrolase

Beta-lactamase inhibitors function by binding to the active site serine residue of the enzyme, either as suicide substrates that form an irreversible covalent bond (e.g., clavulanic acid, tazobactam) or as reversible covalent inhibitors (e.g., avibactam, vaborbactam), thereby preventing the enzyme from degrading co-administered beta-lactam antibiotics (Drawz & Bonomo, 2010; StatPearls, 2023).