Bacterial class A and class C β-lactamase enzymes (Class A/C BLs)

Bacterial class A and class C β-lactamases are serine-based enzymes that represent a major mechanism of antibiotic resistance in Gram-negative bacteria (Bush & Bradford, 2020). These enzymes function by nucleophilically attacking the β-lactam ring of antibiotics like penicillins and cephalosporins, rendering them inactive through hydrolysis (Tooke et al., 2019). Class A enzymes include common penicillinases and extended-spectrum β-lactamases (ESBLs), while Class C enzymes are typically cephalosporinases that can be chromosomally encoded or plasmid-mediated (StatPearls, 2023). Because these enzymes significantly limit the efficacy of standard treatments, they are primary targets for β-lactamase inhibitors such as clavulanic acid, tazobactam, and newer agents like avibactam (Bush & Bradford, 2020). These inhibitors are designed to bind to the enzyme's active site, thereby protecting the companion antibiotic and restoring its ability to inhibit bacterial cell wall synthesis (Tooke et al., 2019). The clinical management of infections caused by bacteria producing these enzymes often requires combination therapies specifically tailored to the enzyme's molecular class.

Other names

Serine β-lactamasesAmbler class A β-lactamasesAmbler class C β-lactamasesPenicillinasesCephalosporinasesAmpC β-lactamasesExtended-spectrum β-lactamases (ESBLs)Serine-active β-lactamases

Inhibition of β-lactamase enzymes through covalent or non-covalent binding to the active site serine residue, preventing the hydrolysis of co-administered β-lactam antibiotics and restoring their antibacterial activity (Bush & Bradford, 2020; Tooke et al., 2019).