The isoleucyl-tRNA synthetase mutation V588F conferring mupirocin resistance in glycopeptide-intermediate Staphylococcus aureus is not associated with a significant fitness burden.
OBJECTIVE
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.
Hurdle
Julian G
JG
Antimicrobial Research Centre and Division of Microbiology, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
O'Neill
Alex J
AJ
Chopra
Ian
I
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005798:Genes, Bacterial / Q000235:genetics*; D007533:Isoleucine-tRNA Ligase / Q000235:genetics*; D016712:Mupirocin / Q000494:pharmacology*; D017354:Point Mutation; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics
D000900:Anti-Bacterial Agents; D016712:Mupirocin; D007533:Isoleucine-tRNA Ligase