AmpC beta-lactamase (AmpC) (AmpC)

AmpC beta-lactamases are a class of enzymes produced by various Gram-negative bacteria that provide resistance to a wide range of beta-lactam antibiotics, including penicillins, most cephalosporins, and monobactams. These enzymes are classified as Ambler Class C and typically utilize a serine-based mechanism for antibiotic hydrolysis (Jacoby, 2009, Clinical Microbiology Reviews). Unlike Class A enzymes, AmpC beta-lactamases are generally not inhibited by classical inhibitors such as clavulanic acid or tazobactam, necessitating the development of next-generation inhibitors like avibactam (Bush & Bradford, 2016, Cold Spring Harbor Perspectives in Medicine). In many bacterial species, AmpC expression is inducible in response to antibiotic exposure, or can become constitutively overexpressed through mutations, a state known as derepression (Tamma et al., 2019, Clinical Infectious Diseases). This resistance profile poses a significant challenge in treating infections caused by organisms like Pseudomonas aeruginosa and Enterobacterales. The emergence of plasmid-mediated AmpC genes has further facilitated their spread among other pathogens like Escherichia coli and Klebsiella pneumoniae (Meini et al., 2019, Reviews in Medical Microbiology). Understanding the regulation and inhibition of AmpC is critical for the effective use of modern antimicrobial therapies.

Other names

Class C beta-lactamaseCephalosporinaseSerine beta-lactamaseCMY-type beta-lactamaseFOX-type beta-lactamaseMOX-type beta-lactamaseLAT-type beta-lactamaseACT-type beta-lactamaseMIR-type beta-lactamase

AmpC beta-lactamases utilize a catalytic serine residue to perform a nucleophilic attack on the beta-lactam ring of antibiotics, leading to the formation of a covalent acyl-enzyme intermediate followed by hydrolysis and inactivation of the drug (Jacoby, 2009, Clinical Microbiology Reviews). Therapeutic inhibitors like avibactam and relebactam function by binding to the active site of the AmpC enzyme, often through a reversible or slowly reversible covalent mechanism, thereby preventing the enzyme from degrading co-administered beta-lactam antibiotics (Bush & Bradford, 2016, Cold Spring Harbor Perspectives in Medicine).