Biochemical basis of mupirocin resistance in strains of Staphylococcus aureus

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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 × 10−1 mg/L in moderately resistant strains it was 1·3 × 10 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.

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