Class D serine β-lactamase (OXA)

Class D serine β-lactamases, commonly known as OXA-type enzymes or oxacillinases, represent a critical mechanism of antibiotic resistance in Gram-negative bacteria, particularly within the ESKAPE pathogens [1][2]. These enzymes are unique among serine β-lactamases due to their requirement for a carboxylated lysine residue in the active site to facilitate the hydrolysis of the β-lactam ring [1][3]. Clinically, the most significant members are the carbapenem-hydrolyzing Class D β-lactamases (CHDLs), such as OXA-48 and OXA-23, which render carbapenems ineffective and severely limit treatment options for hospital-acquired infections [2][3]. Unlike Class A enzymes, Class D β-lactamases are generally poorly inhibited by first-generation inhibitors like clavulanic acid or tazobactam, necessitating the development of next-generation diazabicyclooctane (DBO) and boronate-based inhibitors [4][5]. Recent therapeutic advances, such as the combination of sulbactam and durlobactam, specifically target the OXA-mediated resistance in Acinetobacter baumannii, highlighting the target's importance in modern drug discovery [5].

Other names

OXA-type β-lactamaseOxacillinaseAmbler Class D β-lactamaseCarbapenem-hydrolyzing Class D β-lactamase

Inhibition of the active-site serine residue through covalent or non-covalent binding, preventing the enzymatic degradation of β-lactam antibiotics and restoring their bactericidal activity.