Class A, C, and D serine beta-lactamases (SBLs)

Class A, C, and D serine beta-lactamases are bacterial enzymes that provide resistance to beta-lactam antibiotics by hydrolyzing the amide bond of the beta-lactam ring [1]. These enzymes are characterized by a catalytic mechanism involving a nucleophilic serine residue in the active site, which forms a covalent acyl-enzyme intermediate with the antibiotic [2][3]. Class A enzymes include widespread penicillinases and the clinically significant Klebsiella pneumoniae carbapenemase (KPC); Class C enzymes (AmpC) are typically chromosomal cephalosporinases; and Class D enzymes (OXA) are known for their ability to degrade oxacillin and carbapenems [4][5]. These enzymes are predominantly found in Gram-negative bacteria and represent a major public health threat due to their role in multidrug resistance [6]. To combat this, beta-lactamase inhibitors such as clavulanic acid, avibactam, and vaborbactam are used in combination with antibiotics to neutralize the enzymes and restore antibiotic efficacy [7]. The ongoing evolution of these enzymes, including the emergence of variants resistant to newer inhibitors, necessitates continuous drug development and surveillance [8].

Other names

Ambler Class A, C, and D beta-lactamasesSerine-based beta-lactamasesSerine hydrolasesPenicillinasesCephalosporinasesCarbapenemases

Beta-lactamase inhibitors bind to the active site serine residue of the enzyme, either forming a stable covalent acyl-enzyme intermediate that resists hydrolysis or acting as a transition-state analog, thereby preventing the enzyme from degrading beta-lactam antibiotics.