Biochemical basis of mupirocin resistance in strains of Staphylococcus aureus

J Antimicrob Chemother. 1992 Nov;30(5):587-96. doi: 10.1093/jac/30.5.587.

Abstract

Twenty one strains of Staphylococcus aureus, of varying resistance to mupirocin, were examined in order to determine the mechanism of resistance to this antibiotic; six of these strains were mupirocin sensitive (MIC 0.12-1.0 mg/L) nine moderately resistant strains (MIC 8-256 mg/L) and six highly resistant strains (MIC > 2048 mg/L). Mupirocin showed a time-dependent inhibition of the target enzyme, isoleucyl-tRNA synthetase (IRS); incubation of the antibiotic with this enzyme before adding the substrates markedly increased inhibition in sensitive strains. The IRS I50 values (the antibiotic concentrations which cause a 50% decrease in enzyme activity) correlated well with the MIC values for each strain (P < 0.01). The mean I50 value for sensitive strains was 3.3 x 10(-2) mg/L, in moderately resistant strains it was 1.3 x 10(-1) mg/L and in highly resistant strains it was 7.5 mg/L. No degradation of mupirocin could be detected during extended incubation of the antibiotic with cell free extracts from four resistant S. aureus strains. We conclude that the production of a modified IRS enzyme is the major cause of mupirocin resistance in the strains studied.

MeSH terms

  • Cell-Free System
  • Chromatography, High Pressure Liquid
  • Drug Resistance, Microbial
  • Humans
  • Isoleucine-tRNA Ligase / analysis
  • Isoleucine-tRNA Ligase / antagonists & inhibitors
  • Microbial Sensitivity Tests
  • Mupirocin / pharmacology*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / enzymology

Substances

  • Mupirocin
  • Isoleucine-tRNA Ligase