Class D serine beta-lactamase (OXA)

Class D serine beta-lactamases, commonly referred to as OXA-type enzymes or oxacillinases, are a diverse family of bacterial enzymes that confer resistance to a broad spectrum of beta-lactam antibiotics (Queenan & Bush, 2007). These enzymes are distinguished from other serine beta-lactamases by their unique catalytic mechanism, which requires the carboxylation of a conserved lysine residue to activate the nucleophilic serine (Golemi et al., 2001). While originally identified for their ability to hydrolyze oxacillin, many modern variants have evolved into potent carbapenemases, such as OXA-48 and OXA-23, which degrade "last-resort" carbapenem antibiotics (Poirel et al., 2012). They are predominantly found in problematic Gram-negative pathogens, including Acinetobacter baumannii and Klebsiella pneumoniae, often localized on highly mobile genetic elements (Evans & Amyes, 2014). In clinical practice, these enzymes represent a major therapeutic challenge because they are often poorly inhibited by traditional inhibitors like clavulanic acid. Newer inhibitors, such as avibactam and durlobactam, have been developed to target these enzymes, restoring the efficacy of partner antibiotics (Lahiri et al., 2013; Barnes et al., 2021). However, the rapid diversification of the OXA family and the emergence of mutations that confer resistance to these new inhibitors remain significant concerns for infectious disease management.

Other names

OxacillinaseOXA-type beta-lactamaseAmbler class D beta-lactamaseCarbapenem-hydrolyzing class D beta-lactamaseCHDL

Covalent inhibition of the active-site serine residue, often via a carbamylation-like mechanism in the case of diazabicyclooctanes, which prevents the enzyme from hydrolyzing the beta-lactam ring of co-administered antibiotics (Lahiri et al., 2013).