Mechanisms of resistance to fusidic acid in Staphylococcus aureus.

The biochemical mechanisms of resistance to fusidic acid in Staphylococcus aureus were investigated. Organisms possessing plasmid genes for resistance showed a high basal level of resistance, but could be induced to higher levels after pre-incubation with fusidic acid. This induction occurred rapidly and probably did not depend on gene dosage effects. Mutants resistant to fusidic acid, obtained from plasmid-negative cultures, expressed resistance constitutively. Protein synthesis in cell-free extracts from staphylococci with plasmid-mediated resistance to fusidic acid was as sensitive to fusidic acid as was synthesis in preparations from sensitive organisms; whereas protein synthesis in preparations from a spontaneous fusidic acid resistant mutant was resistant to the antibiotic. None of the resistant strains caused detectable inactivation of fusidic acid and no new derivative of fusidic acid was found in culture extracts of plasmid-possessing organisms grown in the presence of radioactive antibiotic. Expression of plasmid-mediated resistance to fusidic acid was associated with a decrease in the molar ratio of phosphatidylglycerol to lysylphosphatidylglycerol, but the cardiolipin content remained constant.