Class D β-lactamase (OXA)

Class D β-lactamases, frequently referred to as oxacillinases (OXA), are a diverse family of serine-based enzymes that catalyze the hydrolysis of β-lactam antibiotics, thereby conferring bacterial resistance (Bush & Jacoby, 2010). They are distinguished from other serine β-lactamases by their unique active-site chemistry, which requires the carboxylation of a conserved lysine residue to activate the catalytic serine (Leonard et al., 2013). These enzymes are particularly prevalent in Gram-negative pathogens, such as Acinetobacter baumannii and Klebsiella pneumoniae, where they often mediate resistance to carbapenems, the last-resort antibiotics (Poirel et al., 2012). The genes encoding these enzymes, such as blaOXA-48 and blaOXA-23, are frequently located on mobile genetic elements, facilitating their rapid global dissemination (Evans & Amyes, 2014). Because they are poorly inhibited by classical inhibitors like clavulanic acid, they represent a major therapeutic challenge. Recent drug development has focused on next-generation inhibitors like avibactam and durlobactam, which effectively target specific Class D variants to restore antibiotic efficacy (Papp-Wallace et al., 2023).

Other names

OxacillinaseOXA-type β-lactamaseAmbler Class D enzymeSerine-dependent oxacillinase

Inhibitors typically function by forming a covalent, slowly reversible or irreversible acyl-enzyme intermediate with the catalytic serine residue, thereby preventing the enzyme from processing β-lactam antibiotics (Shirley, 2018; Papp-Wallace et al., 2023).