AmpC serine β-lactamase (AmpC)

AmpC serine β-lactamase is a clinically significant bacterial enzyme belonging to Ambler Class C, characterized by its ability to hydrolyze a broad spectrum of β-lactam antibiotics. It is primarily found in Gram-negative bacteria, including the SPACE group (Serratia, Pseudomonas, Acinetobacter, Citrobacter, and Enterobacter), and can be encoded either chromosomally or on mobile plasmids [1.1.1, 1.1.5]. The enzyme functions by utilizing a serine residue in its active site to open the β-lactam ring, thereby inactivating the antibiotic and conferring resistance to penicillins, cephamycins, and most cephalosporins [1.1.2, 1.2.3]. A key feature of AmpC is its inducibility; exposure to certain antibiotics can trigger a massive increase in enzyme production, leading to rapid treatment failure [1.1.1, 1.3.2]. Furthermore, mutations in regulatory genes can lead to stable derepression, where the enzyme is constitutively overproduced [1.2.3, 1.3.3]. While traditional inhibitors like clavulanic acid are ineffective, newer agents such as avibactam and vaborbactam have been developed to target this enzyme, restoring the efficacy of partner β-lactams [1.1.5, 1.2.1].

Other names

Class C beta-lactamaseGroup 1 beta-lactamaseCephalosporinaseblaAmpC

AmpC serine β-lactamase catalyzes the hydrolysis of the β-lactam ring in antibiotics through a serine-mediated nucleophilic attack. The active-site serine residue attacks the carbonyl carbon of the β-lactam ring, forming a covalent acyl-enzyme intermediate. This intermediate is then hydrolyzed by a water molecule, releasing the inactivated antibiotic and regenerating the free enzyme [1.1.1, 1.2.1, 1.2.3].