Ambler Class C beta-lactamase (AmpC) (AmpC)

Ambler Class C beta-lactamases, commonly known as AmpC enzymes, are serine-reactive hydrolases that confer resistance to a wide range of beta-lactam antibiotics, including penicillins, cephalosporins, and monobactams (Jacoby, 2009, Clinical Microbiology Reviews). These enzymes are primarily produced by Gram-negative bacteria such as the "SPACE" organisms (Serratia, Pseudomonas, Acinetobacter, Citrobacter, and Enterobacter) and can be either chromosomally encoded or plasmid-mediated (Bush & Bradford, 2019, Nature Reviews Microbiology). A defining feature of AmpC beta-lactamases is their resistance to classical inhibitors like clavulanic acid, sulbactam, and tazobactam, which distinguishes them from Class A enzymes (StatPearls, 2023, "Beta Lactamase Inhibitors"). In many clinical isolates, AmpC expression is inducible by certain antibiotics like cefoxitin, or can become constitutively overexpressed through mutations in regulatory genes, leading to high-level multidrug resistance (Tamma et al., 2019, Clinical Infectious Diseases). To combat AmpC-mediated resistance, novel inhibitors such as avibactam, relebactam, and vaborbactam have been developed and are used in combination with cephalosporins or carbapenems to restore antimicrobial activity (Meini et al., 2019, Molecules).

Other names

AmpC beta-lactamaseClass C beta-lactamaseCephalosporinaseSerine beta-lactamase Class CEC 3.5.2.6

Beta-lactamase inhibitors (BLIs) such as avibactam and relebactam utilize a covalent, reversible or irreversible binding mechanism to the active-site serine of the AmpC enzyme, effectively blocking the entry and hydrolysis of beta-lactam antibiotics (Bush & Bradford, 2019, Nature Reviews Microbiology).