Class A and Class C beta-lactamase (BL)

Class A and Class C beta-lactamases are a group of bacterial enzymes that serve as a primary defense mechanism against beta-lactam antibiotics, such as penicillins, cephalosporins, and carbapenems [1.3.1, 1.5.1]. These enzymes are classified as serine hydrolases because they utilize a conserved active-site serine residue to facilitate the nucleophilic attack and subsequent hydrolysis of the four-membered beta-lactam ring, rendering the antibiotic therapeutically inactive [1.3.3, 1.5.1]. Class A enzymes include widely disseminated penicillinases (e.g., TEM-1), extended-spectrum beta-lactamases (e.g., CTX-M), and carbapenemases (e.g., KPC), while Class C enzymes (e.g., AmpC) are typically cephalosporinases that are often chromosomally encoded and inducible [1.3.2, 1.5.2]. These enzymes are the primary targets for beta-lactamase inhibitors like tazobactam, avibactam, and relebactam, which are used in combination therapy to protect partner antibiotics from degradation [1.1.1, 1.5.3]. By effectively neutralizing these enzymes, the inhibitors restore the clinical efficacy of beta-lactams against a broad spectrum of multidrug-resistant Gram-negative pathogens, including Enterobacteriaceae and Pseudomonas aeruginosa [1.1.2, 1.4.3].

Other names

Serine beta-lactamaseAmbler class A beta-lactamaseAmbler class C beta-lactamaseAmpCESBLKPCPenicillinaseCephalosporinase

Beta-lactamase inhibition; Covalent acylation of the active site serine; Reversible or irreversible binding to the enzyme active site to prevent antibiotic hydrolysis.