Class A and Class C beta-lactamases (Class A/C BLs)

Class A and Class C beta-lactamases are bacterial enzymes that represent a major mechanism of resistance against beta-lactam antibiotics (Drawz & Bonomo, 2010). These enzymes utilize a catalytic serine residue to nucleophilically attack the beta-lactam ring, leading to the hydrolysis and inactivation of the drug (Bush & Bradford, 2016). Class A enzymes include widespread penicillinases like TEM-1, extended-spectrum beta-lactamases (ESBLs) such as CTX-M, and carbapenemases like KPC (UniProt, 2023). Class C enzymes, often called AmpC beta-lactamases, are typically cephalosporinases that are not well-inhibited by traditional inhibitors like clavulanic acid (StatPearls, 2023). These enzymes are primarily found in Gram-negative pathogens like Klebsiella pneumoniae and Pseudomonas aeruginosa, where they contribute to multidrug-resistant infections (NIH, 2022). In clinical practice, these enzymes are targeted by beta-lactamase inhibitors (BLIs) which are co-administered with antibiotics to protect them from degradation (PubMed, 2019). Newer inhibitors such as avibactam and vaborbactam have been specifically designed to inhibit both Class A and Class C enzymes, restoring the activity of partner drugs like ceftazidime or imipenem (FDA, 2015). The emergence of these enzymes has necessitated the development of novel diagnostic tests and combination therapies to manage life-threatening systemic infections (Nature Reviews Microbiology, 2017).

Other names

Serine beta-lactamasesAmbler Class A beta-lactamasesAmbler Class C beta-lactamasesPenicillinasesCephalosporinasesAmpC beta-lactamases

Beta-lactamase inhibitors bind to the active-site serine residue of Class A and Class C enzymes to form a stable, non-hydrolyzable acyl-enzyme intermediate, thereby preventing the enzyme from degrading co-administered beta-lactam antibiotics (Drawz & Bonomo, 2010).