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

2005; Oxford University Press; Volume: 247; Issue: 2 Linguagem: Inglês

10.1016/j.femsle.2005.05.007

1574-6968

Mirjana Mačvanin, Diarmaid Hughes,

Salmonella and Campylobacter epidemiology

Fusidic acid resistance (FusR) in Salmonella enterica serovar Typhimurium is caused by mutations in fusA, encoding elongation factor G (EF-G). Pleiotropic phenotypes are observed in FusR mutants. Thus, the fusA 1 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 fusA 1–15 allele, (EF-G P413L and T423I) derived from fusA 1 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 fusA 1 allele is associated with sensitivity to ultraviolet light and increased susceptibility to the inhibitory action of several unrelated antibiotic classes (β-lactam, fluoroquinolone, aminoglycoside, rifampicin, and chloramphenicol). The fusA 1–15 allele, in contrast, is less susceptible to UV and to other antibiotics than fusA 1. The hyper-susceptibility to multiple antibiotics associated with fusA 1 and fusA 1–15 is revealed in a novel growth competition assay at sub-MIC concentrations, but not in a standard MIC assay.