Class A and Class D serine beta-lactamases (Class A/D SBLs)

Class A and Class D serine beta-lactamases are bacterial enzymes that serve as a primary defense mechanism against beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems [1]. These enzymes utilize a conserved active-site serine residue to nucleophilically attack the beta-lactam ring, leading to its hydrolysis and the subsequent inactivation of the antibiotic [2]. Class A enzymes include widespread penicillinases like TEM and SHV, as well as the clinically devastating Klebsiella pneumoniae carbapenemase (KPC), which confers resistance to nearly all beta-lactams [1, 3]. Class D enzymes, also known as OXA-type beta-lactamases, are characterized by their ability to hydrolyze oxacillin and are increasingly associated with carbapenem resistance in Acinetobacter baumannii and Enterobacterales [4]. Therapeutic intervention typically involves the use of beta-lactamase inhibitors (BLIs) such as avibactam or relebactam, which protect partner antibiotics from degradation [1, 5]. These combinations are vital for treating multi-drug resistant (MDR) Gram-negative infections in hospital settings [1]. [1] Bush K, Bradford PA. Nat Rev Microbiol. 2019;17(5):295-306. [2] Papp-Wallace KM, et al. Antimicrob Agents Chemother. 2011;55(11):4943-4960. [3] Munoz-Price LS, et al. Lancet Infect Dis. 2013;13(9):785-796. [4] Poirel L, et al. J Antimicrob Chemother. 2012;67(7):1597-1606. [5] Shirley M. Drugs. 2018;78(6):679-692.

Other names

Serine beta-lactamasesAmbler Class A enzymesAmbler Class D enzymesPenicillinasesOXA-type beta-lactamasesKPC-type carbapenemases

Inhibition of the enzyme's catalytic activity through covalent binding to the active-site serine residue, preventing the hydrolysis of co-administered beta-lactam antibiotics and restoring their bactericidal activity.