Class A bacterial beta-lactamase (Class A BL)

Class A bacterial beta-lactamases are a major family of enzymes that confer resistance to a wide range of beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems (Bush & Jacoby, 2010). These enzymes utilize a catalytic serine residue to nucleophilically attack and hydrolyze the beta-lactam ring, thereby inactivating the drug before it can inhibit cell wall synthesis (Ambler, 1980). They are widely distributed among Gram-negative bacteria and are frequently encoded on highly mobile plasmids, which contributes to their rapid global dissemination (PubMed, 2021). Notable members of this class include the TEM and SHV families, the CTX-M extended-spectrum beta-lactamases, and the KPC carbapenemases (NIH, 2023). To combat these enzymes, clinicians use beta-lactamase inhibitors like clavulanic acid or avibactam in combination with antibiotics to protect the antibiotic from degradation (StatPearls, 2023). The evolution of these enzymes remains a significant challenge in infectious disease management, leading to multi-drug resistant bacterial strains.

Other names

Ambler Class A beta-lactamaseSerine beta-lactamasePenicillinaseExtended-spectrum beta-lactamase (ESBL)Klebsiella pneumoniae carbapenemase (KPC)

Beta-lactamase inhibitors bind to the active-site serine residue of the enzyme, forming a covalent acyl-enzyme intermediate that blocks the hydrolysis of co-administered beta-lactam antibiotics (Drawz & Bonomo, 2010).