title: Hyper-susceptibility of a fusidic acid-resistant mutant of Salmonella to different classes of antibiotics.
abstract: Fusidic acid resistance (Fus(R)) in Salmonella enterica serovar Typhimurium is caused by mutations in fusA, encoding elongation factor G (EF-G). Pleiotropic phenotypes are observed in Fus(R) mutants. Thus, the fusA1 allele (EF-G P413L) is associated with slow growth rate, reduced ppGpp and RpoS levels, reduced heme levels, and increased sensitivity to oxidative stress. The fusA1-15 allele, (EF-G P413L and T423I) derived from fusA1 in a selection for growth rate compensation, is partially compensated in each of these phenotypic defects but maintains its resistance to fusidic acid. We show here that the fusA1 allele is associated with sensitivity to ultraviolet light and increased susceptibility to the inhibitory action of several unrelated antibiotic classes (beta-lactam, fluoroquinolone, aminoglycoside, rifampicin, and chloramphenicol). The fusA1-15 allele, in contrast, is less susceptible to UV and to other antibiotics than fusA1. The hyper-susceptibility to multiple antibiotics associated with fusA1 and fusA1-15 is revealed in a novel growth competition assay at sub-MIC concentrations, but not in a standard MIC assay.
authors.affiliation: Microbiology Programme, Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Box 596, S-75124 Uppsala, Sweden.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Macvanin
authors.forename: Diarmaid
authors.initials: D
authors.lastname: Hughes
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002701:Chloramphenicol / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology; D005672:Fusidic Acid / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012293:Rifampin / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects*; D014466:Ultraviolet Rays; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D047090:beta-Lactams; D005672:Fusidic Acid; D002701:Chloramphenicol; D012293:Rifampin