Ambler Class A beta-lactamase (Class A BL) (Class A BL)

Ambler Class A beta-lactamases are a diverse group of enzymes produced by bacteria that provide resistance to beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems (Bush & Jacoby, 2010). These enzymes are serine-hydrolases that utilize a conserved active-site serine residue to nucleophilically attack and hydrolyze the four-membered beta-lactam ring, rendering the antibiotic inactive (Tooke et al., 2019). Class A enzymes are the most common beta-lactamases and include clinically significant variants such as TEM, SHV, and CTX-M extended-spectrum beta-lactamases (ESBLs), as well as the Klebsiella pneumoniae carbapenemase (KPC) (Ambler, 1980; StatPearls, 2023). They are frequently encoded on mobile genetic elements like plasmids, facilitating rapid spread among Gram-negative pathogens (PubMed, PMC7011721). Therapeutic management often involves combining beta-lactam antibiotics with inhibitors like clavulanic acid, tazobactam, or newer non-beta-lactam inhibitors like avibactam and vaborbactam to restore antibiotic efficacy (NIH, 2023). The ongoing evolution of these enzymes, leading to resistance against even the newest inhibitors, remains a critical challenge in treating multi-drug resistant infections (Nature Reviews Microbiology, 2022).

Other names

Serine beta-lactamasePenicillinaseExtended-spectrum beta-lactamase (ESBL)CarbapenemaseKPCTEMSHVCTX-M

Inhibition of the enzyme's catalytic activity through covalent or non-covalent binding to the active site, preventing the hydrolysis of co-administered beta-lactam antibiotics (StatPearls, 2023).