Julian G Hurdle1, Alex J O'Neill, Ian Chopra. 1. Antimicrobial Research Centre and Division of Microbiology, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
Abstract
OBJECTIVES AND METHODS: Failure to eradicate nasal carriage of a glycopeptide-intermediate Staphylococcus aureus (strain GISA-2) with mupirocin was recently attributed to a mutation that confers low-level mupirocin resistance. To identify this mutation the ileS genes of GISA-2 and its mupirocin-susceptible progenitor GISA-1 were sequenced. For comparison, the ileS genes of 10 laboratory-derived mupirocin-resistant mutants of the GISA strain Mu50 were also examined. The fitness of GISA-2 and mupirocin-susceptible GISA-1, as well as Mu50 and its mupirocin-resistant derivatives, were compared by evaluation of growth rates and performance in mixed-culture competition assays. RESULTS: The point mutation V588F in the isoleucyl-tRNA synthetase was identified from the ileS sequences of GISA-2 and mupirocin-resistant mutants of Mu50. The V588F mutation was not associated with a significant fitness burden. CONCLUSIONS: The low fitness cost of the V588F substitution in isoleucyl-tRNA synthetase is consistent with the frequent appearance and maintenance of this mutation in mupirocin-resistant clinical isolates, including GISA-2.
OBJECTIVES AND METHODS: Failure to eradicate nasal carriage of a glycopeptide-intermediate Staphylococcus aureus (strain GISA-2) with mupirocin was recently attributed to a mutation that confers low-level mupirocin resistance. To identify this mutation the ileS genes of GISA-2 and its mupirocin-susceptible progenitor GISA-1 were sequenced. For comparison, the ileS genes of 10 laboratory-derived mupirocin-resistant mutants of the GISA strain Mu50 were also examined. The fitness of GISA-2 and mupirocin-susceptible GISA-1, as well as Mu50 and its mupirocin-resistant derivatives, were compared by evaluation of growth rates and performance in mixed-culture competition assays. RESULTS: The point mutation V588F in the isoleucyl-tRNA synthetase was identified from the ileS sequences of GISA-2 and mupirocin-resistant mutants of Mu50. The V588F mutation was not associated with a significant fitness burden. CONCLUSIONS: The low fitness cost of the V588F substitution in isoleucyl-tRNA synthetase is consistent with the frequent appearance and maintenance of this mutation in mupirocin-resistant clinical isolates, including GISA-2.
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