Ambler class A and C serine beta-lactamases (SBL (Class A and C))

Ambler class A and C serine beta-lactamases are critical bacterial enzymes that mediate resistance to beta-lactam antibiotics, the most widely used class of antibacterials [1, 4]. These enzymes function as serine hydrolases, utilizing a conserved active-site serine residue to catalyze the hydrolytic opening of the four-membered beta-lactam ring, which renders the antibiotic inactive before it can reach its target, the penicillin-binding proteins [5, 11]. Class A enzymes include common penicillinases, extended-spectrum beta-lactamases (ESBLs) like CTX-M, and potent carbapenemases such as KPC, while Class C enzymes (AmpC) are primarily cephalosporinases that are often chromosomally encoded and inducible [1, 9, 12]. Because these enzymes are frequently carried on mobile genetic elements like plasmids, they spread rapidly among clinically significant Gram-negative pathogens, including Klebsiella pneumoniae and Escherichia coli [3, 15]. Therapeutic strategies involve the use of beta-lactamase inhibitors, such as clavulanic acid, tazobactam, or the newer non-beta-lactam inhibitor avibactam, which are co-administered with antibiotics to protect them from degradation and restore their clinical efficacy [7, 8, 10]. The ongoing evolution of these enzymes, including the development of variants resistant to current inhibitors, remains a major challenge in the treatment of multidrug-resistant bacterial infections [3, 11].

Other names

Class A beta-lactamasesClass C beta-lactamasesSerine beta-lactamasesPenicillinasesCephalosporinasesAmpC beta-lactamasesExtended-spectrum beta-lactamases (ESBLs)Klebsiella pneumoniae carbapenemases (KPCs)

Drugs targeting these enzymes act as beta-lactamase inhibitors (BLIs), which bind to the active-site serine residue through covalent acylation (suicide inhibition) or reversible covalent binding, thereby preventing the enzyme from hydrolyzing co-administered beta-lactam antibiotics [1, 7, 8].