Ambler class D serine β-lactamase (OXA)

Ambler class D serine β-lactamases, commonly referred to as OXA-type enzymes, are a diverse family of bacterial enzymes that mediate resistance to β-lactam antibiotics by hydrolyzing the amide bond of the β-lactam ring (Poirel et al., 2012, https://doi.org/10.1128/cmr.00018-12). Originally identified for their ability to degrade oxacillin, these enzymes have evolved into potent carbapenemases, particularly in Gram-negative pathogens like Acinetobacter baumannii and Klebsiella pneumoniae (Evans & Amyes, 2014, https://doi.org/10.1128/cmr.00117-13). Their biological function is primarily defensive, allowing bacteria to survive in the presence of penicillins, cephalosporins, and carbapenems. In clinical settings, they are major contributors to treatment failure in healthcare-associated infections (Walther-Rasmussen & Høiby, 2006, https://doi.org/10.1093/jac/dkl010). Therapeutic intervention typically involves combining a β-lactam antibiotic with a β-lactamase inhibitor, such as avibactam or durlobactam, which binds to the active-site serine to neutralize the enzyme (Papp-Wallace et al., 2020, https://doi.org/10.1128/aac.01017-20). However, the extreme sequence diversity of Class D enzymes presents a significant challenge for drug development, as many variants exhibit unique resistance profiles (Leonard et al., 2013, https://doi.org/10.1021/cr300329n).

Other names

OXA-type β-lactamaseOxacillinaseClass D β-lactamaseSerine-type β-lactamase class D

Inhibition of the β-lactamase enzyme through covalent or non-covalent binding to the active site, preventing the hydrolysis of co-administered β-lactam antibiotics (Papp-Wallace et al., 2020, https://doi.org/10.1128/aac.01017-20).