Class A and Class C bacterial beta-lactamases (Class A and C BLs)

Class A and Class C bacterial beta-lactamases are enzymes produced by various Gram-negative and Gram-positive bacteria that confer resistance to beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems [1, 2]. These enzymes function by hydrolyzing the four-membered beta-lactam ring, thereby inactivating the antibiotic before it can reach its target, the penicillin-binding proteins [2, 3]. Class A enzymes include common penicillinases, extended-spectrum beta-lactamases (ESBLs) like CTX-M, and carbapenemases such as KPC [1]. Class C enzymes, often referred to as AmpC beta-lactamases, are typically resistant to traditional inhibitors like clavulanic acid and are frequently overexpressed in organisms like Pseudomonas aeruginosa and Enterobacter species [1, 3]. Because these enzymes are primary drivers of multi-drug resistance in clinical settings, they are critical therapeutic targets for beta-lactamase inhibitors [4]. Modern inhibitors such as avibactam and relebactam are designed to restore the efficacy of partner antibiotics by binding to the active site serine of these enzymes [1, 4]. Targeting these beta-lactamases is essential for treating severe infections caused by carbapenem-resistant Enterobacterales (CRE) and other resistant pathogens [1].

Other names

Serine beta-lactamasesAmbler Class A beta-lactamasesAmbler Class C beta-lactamasesPenicillinasesCephalosporinasesAmpC beta-lactamasesExtended-spectrum beta-lactamases (ESBLs)Klebsiella pneumoniae carbapenemases (KPCs)

Inhibition of beta-lactamase activity through covalent or non-covalent binding to the active site serine residue, preventing the hydrolysis of co-administered beta-lactam antibiotics [1, 3].