title: Mutant ribosomes can generate dominant kirromycin resistance.
abstract: Mutations in the two genes for EF-Tu in Salmonella typhimurium and Escherichia coli, tufA and tufB, can confer resistance to the antibiotic kirromycin. Kirromycin resistance is a recessive phenotype expressed when both tuf genes are mutant. We describe a new kirromycin-resistant phenotype dominant to the effect of wild-type EF-Tu. Strains carrying a single kirromycin-resistant tuf mutation and an error-restrictive, streptomycin-resistant rpsL mutation are resistant to high levels of kirromycin, even when the other tuf gene is wild type. This phenotype is dependent on error-restrictive mutations and is not expressed with nonrestrictive streptomycin-resistant mutations. Kirromycin resistance is also expressed at a low level in the absence of any mutant EF-Tu. These novel phenotypes exist as a result of differences in the interactions of mutant and wild-type EF-Tu with the mutant ribosomes. The restrictive ribosomes have a relatively poor interaction with wild-type EF-Tu and are thus more easily saturated with mutant kirromycin-resistant EF-Tu. In addition, the mutant ribosomes are inherently kirromycin resistant and support a significantly faster EF-Tu cycle time in the presence of the antibiotic than do wild-type ribosomes. A second phenotype associated with combinations of rpsL and error-prone tuf mutations is a reduction in the level of resistance to streptomycin.
authors.affiliation: Department of Molecular Biology, Biomedical Center, Uppsala, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Tubulekas
authors.forename: R H
authors.initials: RH
authors.lastname: Buckingham
authors.forename: D
authors.initials: D
authors.lastname: Hughes
mesh_terms: D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D029968:Escherichia coli Proteins; D005798:Genes, Bacterial; D007700:Kinetics; D008969:Molecular Sequence Data; D010444:Peptide Elongation Factor Tu / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011728:Pyridones / Q000494:pharmacology; D000091243:Ribosomal Protein S9; D012270:Ribosomes / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics*; D013045:Species Specificity; D013307:Streptomycin
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D011728:Pyridones; D000091243:Ribosomal Protein S9; C000717190:RpsI protein, E coli; D010444:Peptide Elongation Factor Tu; C008536:mocimycin; D013307:Streptomycin