Hyper-susceptibility of a fusidic acid-resistant mutant of Salmonella to different classes of antibiotics

Fusidic acid resistance (FUSR) in Salmonella enterica serovar Typhimurium is caused by mutations in jusA, encoding elongation factor G (EF-G). Pleiotropic phenotypes are observed in Fus(R) mutants. Thus, the fusA1 allete (EF-G P413L) is associated with slow growth rate, reduced ppGpp and RpoS levels, reduced heme levels, and increased sensitivity to oxidative stress. The fusA 1-15 allele, (EF-G P413L and T4231) 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 (P-lactam, fluoroquinolone, aminoglycoside, rifampicin, and chloramphenicol). The fusA 1-15 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. (c) 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.