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JAC Advance Access originally published online on December 4, 2003
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Journal of Antimicrobial Chemotherapy (2004) 53, 102-104
© 2004 The British Society for Antimicrobial Chemotherapy

The isoleucyl-tRNA synthetase mutation V588F conferring mupirocin resistance in glycopeptide-intermediate Staphylococcus aureus is not associated with a significant fitness burden

Julian G. Hurdle, Alex J. O’Neill and Ian Chopra*

Antimicrobial Research Centre and Division of Microbiology, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK

Received 31 July 2003; returned 29 September 2003; revised 29 September 2003; accepted 13 October 2003

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.

Keywords: GISA, mupirocin-resistant Staphylococcus aureus

* Corresponding author. Tel: +44-113-343-5604; Fax: +44-113-343-3167; E-mail: i.chopra{at}leeds.ac.uk


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