Serine beta-lactamase (Ambler classes A, C, and D) (SBLs)

Serine beta-lactamases (SBLs) are bacterial enzymes that represent a primary mechanism of resistance against beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems (Bush K, Bradford PA. Nat Rev Microbiol. 2019). According to the Ambler classification system, these enzymes are categorized into Classes A, C, and D based on their use of a conserved serine residue in the active site to nucleophilically attack and hydrolyze the beta-lactam ring (Ambler RP. Philos Trans R Soc Lond B Biol Sci. 1980). Class A includes common enzymes like TEM, SHV, and the KPC carbapenemase; Class C comprises AmpC cephalosporinases; and Class D includes OXA-type enzymes often found in Acinetobacter and Enterobacterales (Drawz SM, Bonomo RA. Clin Microbiol Rev. 2010). These enzymes are frequently encoded on mobile genetic elements, facilitating their rapid spread among clinical pathogens and complicating the treatment of healthcare-associated infections. Therapeutic management often relies on beta-lactamase inhibitors (BLIs) which, when co-administered with an antibiotic, protect the drug from degradation. Recent advancements have led to the development of diazabicyclooctane (DBO) and boronate-based inhibitors that effectively target a broader spectrum of SBLs, including those previously resistant to traditional inhibitors (StatPearls, 'Beta Lactamase Inhibitors', 2023).

Other names

Serine-based beta-lactamasesClass A beta-lactamasesClass C beta-lactamasesClass D beta-lactamasesPenicillinasesCephalosporinasesCarbapenemases

Inhibition of the enzyme active site through covalent or non-covalent binding to the catalytic serine residue, preventing the hydrolysis of beta-lactam antibiotics (Drawz SM, Bonomo RA. Clin Microbiol Rev. 2010).