Resistance of Escherichia coli to penicillins: fine-structure mapping and dominance of chromosomal beta-lactamase mutations

Abstract

Seven E. coli K-12 mutants with a lowered chromosomal .beta.-lactamase activity were analyzed genetically. The .beta.-lactamase-negative mutants isolated from ampA1-carrying strains (resistant to 10 .mu.g of ampicillin/ml) all carried genetic lesions very close to the ampA1 mutation, which was still present. In an earlier report, 2 of the mutations mediating a .beta.-lactamase-negative phenotype probably were located in the structural gene for .beta.-lactamase, designated ampC. All .beta.-lactamase-negative mutants studied here were probably altered in ampC. The relative order of ampC mutations was (ampC1, ampC8)-ampC9-(ampC12, ampC14)-ampC11, and the gene order was ampC-ampA-purA. The ampA1 allele was dominant over its wild-type allele but acted only cis and not trans, suggesting that ampA is the promoter or operator region for ampC. A gene dosage effect was found for strains homozygous for ampA+ ampC+ or ampA1 ampC+. Heterozygotes carrying the ampC8 allele on the chromosome showed an apparent derepression of the episomal ampC allele, suggesting a role for .beta.-lactamase in its own regulation.