Class A and Class B beta-lactamases (Class A/B BLAs)

Class A and Class B beta-lactamases are bacterial enzymes that provide resistance to beta-lactam antibiotics by hydrolyzing the amide bond of the beta-lactam ring (Bush & Jacoby, 2010). Class A enzymes, such as the Klebsiella pneumoniae carbapenemase (KPC), utilize a serine-based mechanism and are widely distributed among Gram-negative pathogens, often leading to resistance against penicillins and cephalosporins (Bonomo, 2017). Class B enzymes, also known as metallo-beta-lactamases (MBLs) like New Delhi metallo-beta-lactamase (NDM), require zinc ions for catalysis and are capable of degrading nearly all beta-lactam antibiotics, including carbapenems (Tooke et al., 2019). These enzymes are significant clinical targets because their expression often results in multidrug-resistant (MDR) infections that are difficult to treat with standard therapies (StatPearls, 2023). Drug development focuses on beta-lactamase inhibitors (BLIs) that can be paired with antibiotics to neutralize these enzymes and restore the efficacy of the treatment (PubChem, 2024). While several inhibitors effectively target Class A enzymes, Class B enzymes remain a major therapeutic challenge due to their distinct structural and catalytic properties (NIH, 2022).

Other names

Serine beta-lactamases (Class A)Metallo-beta-lactamases (Class B)PenicillinasesCarbapenemasesMBLsAmbler Class AAmbler Class B

Inhibition of beta-lactamase activity through the formation of a stable acyl-enzyme intermediate (Class A) or through zinc-coordination/sequestration (Class B) to prevent antibiotic degradation (Tooke et al., 2019; Bonomo, 2017).