Class A and Class C serine beta-lactamases (Class A and C SBLs)

Class A and Class C serine beta-lactamases are critical bacterial enzymes that mediate resistance to a wide range of beta-lactam antibiotics, including penicillins, cephalosporins, and in some cases, carbapenems. These enzymes function by using a conserved active-site serine residue to nucleophilically attack and hydrolyze the amide bond of the beta-lactam ring, thereby inactivating the drug before it can reach its penicillin-binding protein targets (Bush & Bradford, 2016). Class A enzymes, such as TEM-1, SHV-1, and the carbapenemase KPC, are frequently plasmid-encoded and highly prevalent in Enterobacteriaceae, while Class C enzymes (AmpC) are often chromosomally encoded and can be induced or constitutively overexpressed in organisms like Pseudomonas aeruginosa (Papp-Wallace et al., 2011). Because of their central role in multi-drug resistance, these enzymes are the primary targets for beta-lactamase inhibitors like clavulanic acid and newer diazabicyclooctane (DBO) inhibitors like avibactam (Shirley, 2018). Therapeutic strategies typically involve combination therapies that pair a beta-lactam antibiotic with an inhibitor to protect the antibiotic from enzymatic degradation and restore its clinical efficacy against resistant Gram-negative pathogens (Drawz & Bonomo, 2010).

Other names

Ambler Class A beta-lactamasesAmbler Class C beta-lactamasesSerine beta-lactamasesPenicillinasesCephalosporinasesAmpC beta-lactamasesSerine-based beta-lactamases

Inhibition of the enzyme's catalytic serine residue, typically through the formation of a stable acyl-enzyme intermediate or a covalent bond, which prevents the enzyme from degrading co-administered beta-lactam antibiotics.