Bacterial class A and class C serine beta-lactamase (Class A/C SBL)

Bacterial class A and class C serine beta-lactamases are critical enzymes that mediate antibiotic resistance in Gram-negative and Gram-positive bacteria by hydrolyzing the four-membered beta-lactam ring of various antibiotics (Bush & Bradford, 2016, Cold Spring Harb Perspect Med). Class A enzymes are highly diverse, encompassing narrow-spectrum penicillinases such as TEM and SHV, extended-spectrum beta-lactamases like CTX-M, and potent carbapenemases such as KPC, while Class C enzymes (AmpC) primarily target cephalosporins (Papp-Wallace et al., 2011, Science). These enzymes utilize a conserved active-site serine residue to initiate a nucleophilic attack on the antibiotic's carbonyl group, forming a covalent acyl-enzyme intermediate that is subsequently hydrolyzed to release the inactive drug (Tooke et al., 2019, J Mol Biol). Because they neutralize first-line treatments like penicillins and cephalosporins, they are primary targets for drug development. Therapeutic strategies often involve the use of beta-lactamase inhibitors such as avibactam, relebactam, or vaborbactam, which are co-administered with a beta-lactam antibiotic to protect it from degradation and restore its antimicrobial activity (Shirley, 2018, Drugs). The clinical significance of these enzymes is profound, as they are a primary driver of multi-drug resistance in pathogens like Klebsiella pneumoniae and Escherichia coli (Jacoby, 2009, Clin Microbiol Rev). The rapid evolution and horizontal gene transfer of these enzymes continue to pose a major threat to global public health by limiting effective treatment options for serious infections.

Other names

Ambler class A beta-lactamaseAmbler class C beta-lactamaseSerine beta-lactamasePenicillinaseCephalosporinaseAmpC beta-lactamase

Inhibition of beta-lactamase activity through covalent or non-covalent binding to the active-site serine residue, preventing the hydrolysis of co-administered beta-lactam antibiotics.