Beta-lactamase OXA-48 (OXA-48) (OXA-48)

Beta-lactamase OXA-48 (OXA-48) is a carbapenem-hydrolyzing class D enzyme that represents a major mechanism of antibiotic resistance in Gram-negative bacteria, particularly Enterobacterales such as Klebsiella pneumoniae and Escherichia coli [1, 10]. First identified in 2001, it has since spread globally, primarily through the horizontal transfer of highly mobile IncL plasmids [13, 14]. Biologically, OXA-48 acts as a serine hydrolase that efficiently degrades penicillins and early-generation cephalosporins, while providing low-to-moderate resistance to last-resort carbapenem antibiotics [1, 6]. A significant clinical challenge associated with OXA-48 is its ability to confer resistance that often falls below standard laboratory detection thresholds, leading to potential treatment failures [8, 16]. Furthermore, the enzyme is intrinsically resistant to traditional beta-lactamase inhibitors like clavulanic acid and tazobactam [1, 13]. Modern therapeutic approaches focus on combining beta-lactam antibiotics with novel inhibitors such as avibactam or durlobactam to overcome OXA-48-mediated resistance [2, 5, 10].

Other names

Oxacillinase-48Class D carbapenemaseCarbapenem-hydrolyzing class D beta-lactamaseCHDL

OXA-48 functions as a serine hydrolase that inactivates beta-lactam antibiotics by catalyzing the hydrolysis of the beta-lactam ring. The reaction proceeds through the formation of a covalent acyl-enzyme intermediate with an active-site serine residue (Ser70). A unique feature of this class D enzyme is the requirement for a carboxylated lysine residue (Lys73), which acts as a general base to activate the deacylating water molecule [1, 6, 10].