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

Serine beta-lactamases (SBLs) are bacterial enzymes classified into Ambler Classes A, C, and D that confer resistance to beta-lactam antibiotics by hydrolyzing the amide bond of the beta-lactam ring (Bush & Bradford, 2016, Cold Spring Harb Perspect Med). These enzymes utilize a catalytic serine residue to perform a nucleophilic attack on the antibiotic, leading to its inactivation (Tooke et al., 2019, J Mol Biol). SBLs are widely distributed among Gram-negative pathogens and are responsible for resistance to penicillins, cephalosporins, and carbapenems, posing a significant threat to global health (Bonomo, 2017, Cold Spring Harb Perspect Med). Class A enzymes include the widespread TEM, SHV, and KPC variants, while Class C (AmpC) and Class D (OXA) enzymes further expand the resistance profile of bacteria (Bush, 2018, Expert Opin Ther Targets). Therapeutic strategies involve the use of beta-lactamase inhibitors, such as clavulanic acid, tazobactam, or the newer diazabicyclooctane (DBO) inhibitor avibactam, which bind to the active site serine to prevent antibiotic degradation (Papp-Wallace et al., 2011, Antimicrob Agents Chemother). These inhibitors are typically administered in combination with a beta-lactam antibiotic to restore its efficacy against resistant strains (Drawz & Bonomo, 2010, Clin Microbiol Rev).

Other names

Serine-based beta-lactamasesAmbler Class A beta-lactamasesAmbler Class C beta-lactamasesAmbler Class D beta-lactamasesPenicillinasesCephalosporinasesOxacillinases

Beta-lactamase inhibitors bind to the active site of the serine beta-lactamase enzyme, often forming a stable covalent intermediate that prevents the enzyme from degrading beta-lactam antibiotics, thereby restoring the efficacy of the co-administered antibiotic (Drawz & Bonomo, 2010, Clin Microbiol Rev).