Ambler class C β-lactamase (Class C β-lactamase)

Ambler class C β-lactamases, also known as AmpC β-lactamases or cephalosporinases, are serine-based enzymes produced by gram-negative bacteria that hydrolyze the β-lactam ring in antibiotics such as penicillins, most cephalosporins (except cefepime), cephamycins like cefoxitin and cefotetan, and monobactams like aztreonam, conferring resistance to these drugs. They are classified within the Ambler molecular scheme based on amino acid sequence homology, sharing conserved motifs like 64SXSK, 150YXN, and 315KTG, and are chromosomally encoded in many Enterobacteriaceae (e.g., Citrobacter, Serratia, Enterobacter) with inducible expression, though plasmid-mediated variants like CMY-2 and FOX-1 are common in clinical isolates. These enzymes play a critical role in bacterial multidrug resistance, particularly in hospital-acquired infections caused by pathogens like Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. Therapeutically, they are targeted by β-lactam/β-lactamase inhibitor combinations such as ceftazidime-avibactam, where avibactam covalently inhibits the active-site serine, protecting the partner β-lactam from hydrolysis. Challenges include their poor inhibition by older inhibitors like clavulanate and the rise of extended-spectrum variants contributing to carbapenem-resistant infections.

Other names

AmpC β-lactamaseAmpC enzymeclass C cephalosporinasegroup 1 cephalosporinase

Serine-based hydrolysis mechanism (classes A, C, D); inhibition by β-lactamase inhibitors like avibactam to restore β-lactam antibiotic activity