OXA-48 serine β-lactamase (OXA-48)

OXA-48 serine β-lactamase is a carbapenem-hydrolyzing class D enzyme that represents a significant mechanism of antibiotic resistance in Gram-negative bacteria, particularly Enterobacterales such as Klebsiella pneumoniae and Escherichia coli. First identified in 2001, it has since spread globally, primarily through the horizontal transfer of highly conserved IncL plasmids. The enzyme functions as a serine hydrolase, utilizing an active-site serine to attack the β-lactam ring of antibiotics, forming a covalent acyl-enzyme intermediate that is subsequently hydrolyzed to render the drug inactive. Unlike many other carbapenemases, OXA-48 typically confers high-level resistance to penicillins but only low-level resistance to carbapenems, and it generally spares expanded-spectrum cephalosporins, a profile that often complicates its detection in clinical laboratories. Therapeutic management of OXA-48-producing infections often relies on the use of novel β-lactamase inhibitors like avibactam, which can covalently bind and neutralize the enzyme, thereby restoring the efficacy of partner antibiotics such as ceftazidime.

Other names

Oxacillinase-48Carbapenem-hydrolyzing class D β-lactamaseCHDLblaOXA-48

OXA-48 operates via a serine-based catalytic mechanism where the active-site serine (S70) performs a nucleophilic attack on the carbonyl group of the β-lactam ring to form a covalent acyl-enzyme intermediate; this intermediate is then hydrolyzed by a water molecule activated by a carboxylated lysine (K73), releasing the inactivated antibiotic. Therapeutic inhibitors like avibactam act by forming a stable, slowly reversible covalent bond with the active-site serine, effectively sequestering the enzyme and preventing it from degrading β-lactam antibiotics.