Ambler Class D beta-lactamase (OXA) (OXA)

Ambler Class D beta-lactamases, also known as oxacillinases (OXA), are a diverse group of serine-based enzymes that play a critical role in bacterial resistance to beta-lactam antibiotics. These enzymes are characterized by their ability to hydrolyze oxacillin and, increasingly, carbapenems, which are often reserved for severe, multidrug-resistant infections (Poirel et al., 2010, PMID: 20211898). Unlike Class A and C enzymes, Class D beta-lactamases utilize a unique carboxylated lysine residue in their active site to facilitate the nucleophilic attack on the beta-lactam ring (Leonard et al., 2013, PMID: 23410018). They are predominantly found in problematic Gram-negative pathogens such as Acinetobacter baumannii and Klebsiella pneumoniae, where they are often encoded on mobile genetic elements (Bush & Bradford, 2019, PMID: 30872834). Because traditional inhibitors like clavulanic acid are largely ineffective against them, Class D enzymes represent a significant therapeutic challenge. Recent drug development has introduced novel non-beta-lactam inhibitors, such as avibactam and durlobactam, which effectively target specific OXA variants to restore the efficacy of partner antibiotics (Walther-Rasmussen & Høiby, 2006, PMID: 16533821).

Other names

OxacillinaseOXA-type beta-lactamaseClass D serine beta-lactamaseCarbapenem-hydrolyzing class D beta-lactamase (CHDL)

Inhibition of the beta-lactamase enzyme through covalent binding to the active-site serine residue, often via a reversible or slowly reversible carbamylation mechanism (for diazabicyclooctanes) or boronic acid-serine adduct formation (for boronates), which prevents the enzyme from degrading co-administered beta-lactam antibiotics and restores their bactericidal activity (Bush & Bradford, 2019, PMID: 30872834).