Chromosomal beta-lactam resistance in enterobacteria.
Most enterobacterial species carry a chromosomal ampC beta-lactamase gene. In Escherichia coli and Shigella, expression from ampC is non-inducible and the beta-lactamase is synthesized at low levels. Mutations leading to increased beta-lactamase synthesis occur rather infrequently, making resistance to modern cephalosporins a rare event in these species. In other enterobacteria and Pseudomonas, ampC beta-lactamase synthesis is induced by beta-lactams. In Enterobacter cloacae, Citrobacter freundii and probably also in other species with inducible beta-lactamase expression, ampC is regulated by at least two genes, ampR and ampD. Mutations affecting ampR abolish beta-lactamase inducibility, and mutants devoid of ampR, produce ampC beta-lactamase at low constitutive levels. Mutations in ampD lead to constitutive overproduction of inducible beta-lactamase if an intact ampR protein is present in the cell. The latter type of mutations occur at a high frequency and result in clinical resistance to several third-generation cephalosporins.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D002876:Chromosomes, Bacterial; D004352:Drug Resistance, Microbial; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D004790:Enzyme Induction; D005798:Genes, Bacterial; D009154:Mutation; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics*; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001618:beta-Lactamases