Class A and Class C beta-lactamase enzymes (Class A/C BLs)

Class A and Class C beta-lactamases are serine-based enzymes produced by bacteria to neutralize beta-lactam antibiotics, such as penicillins and cephalosporins. These enzymes function by hydrolyzing the amide bond of the beta-lactam ring, rendering the antibiotic incapable of inhibiting bacterial cell wall synthesis (Bush & Bradford, 2016). Class A enzymes include common penicillinases, extended-spectrum beta-lactamases (ESBLs), and carbapenemases like KPC, which are major drivers of resistance in Enterobacteriaceae (StatPearls, 2023). Class C enzymes, or AmpC beta-lactamases, are primarily cephalosporinases that are often resistant to traditional inhibitors like clavulanic acid and can be induced by certain antibiotics (Meini et al., 2019). In clinical settings, these enzymes are significant therapeutic targets because they protect pathogens from the most commonly used classes of antibiotics. To overcome this resistance, drugs are formulated as combinations of a beta-lactam antibiotic and a beta-lactamase inhibitor, such as ceftazidime-avibactam or imipenem-relebactam (Tooke et al., 2019). These inhibitors bind to the active site of the enzymes, restoring the efficacy of the antibiotic against multi-drug resistant infections. The ongoing evolution of these enzymes continues to challenge drug development, necessitating the creation of broader-spectrum inhibitors.

Other names

Serine beta-lactamasesAmbler Class A beta-lactamasesAmbler Class C beta-lactamasesPenicillinasesCephalosporinasesAmpC beta-lactamasesESBLs (Extended-spectrum beta-lactamases)

Inhibition of the serine-dependent hydrolytic activity of beta-lactamase enzymes through covalent or reversible binding to the active site, thereby protecting co-administered beta-lactam antibiotics from degradation.