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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.

frontiers in microbiology

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