Staphylococcus aureus is an important pathogen in hospital and community
infections.
Fusidic acid is particularly effective in treating skin and
wound infections caused by staphylococci. The purpose of our study was to clarify the effect of
fusidic acid on the biofilm formation and α-toxin expression of S. aureus at subinhibitory concentrations [1/64, 1/32, and 1/16 × minimum inhibitory concentration (MIC)]. A total of 504 genes greater than a twofold or less than twofold change in expression of S. aureus effected by subinhibitory concentrations of
fusidic acid were found, including 232 up-regulated genes and 272 down-regulated genes, which were determined by transcriptome sequencing. Our results showed subinhibitory concentrations of
fusidic acid significantly inhibited the expression of hla, spa, icaA, and cidA at the
mRNA level in clinical S. aureus strains tested. And subinhibitory concentrations of
fusidic acid can significantly reduce the
hemolysis activity and α-toxin production of S. aureus. In addition, the subinhibitory concentrations of
fusidic acid significantly inhibited biofilm formation,
autolysis, cell aggregation, and
polysaccharide intercellular adhesin (PIA) production of S. aureus. Moreover,
fusidic acid effectively reduces the damage of mouse skin lesion area. Furthermore,
fusidic acid reduced the expression of the two-component regulatory system saeRS and staphylococcal accessory gene regulator (sarA). In conclusion, our results suggested that the subinhibitory concentrations of
fusidic acid may reduce the virulence of S. aureus by down-regulating sarA and saeRS to reduce biofilm formation and α-toxin expression, which will provide a theoretical basis for the clinical treatment of S. aureus
infection. This is the first report that
fusidic acid has an inhibitory effect on the virulence of S. aureus, and this broadens the clinical application of
fusidic acid.