Biochemical basis of mnpirodn resistance in strains of Staphylococcus awreus

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 I n values (the antibiotic concentrations which cause a 50% decrease in enzyme activity) correlated well with the MIC values for each strain {P < 001). The mean lx value for sensitive strains was 3-3 x 10~2 mg/L, in moder-ately resistant strains it was 1-3 x 10~ ' mg/L and in highly resistant strains it was 7-5 mg/L. No degradation of mupirocin could be detected during extended incuba-tion 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