The Sub-Inhibitory Concentrations of Fusidic Acid Reduce the Virulence of <i>S. aureus</i> by Reducing the Expression of Virulence-Associated Genes

Abstract

Background: Staphylococcus aureus is an important pathogen for hospital and community infections. Fusidic acid is particularly effective in treating skin and wound infections caused by Staphylococci. Methods: The effect of fusidic acid on the transcription of S. aureus was studied by transcriptome sequencing. The effect of the sub-inhibitory concentrations of fusidic acid on α-toxin and virulence expression of S. aureus by detecting the hemolytic activity, enzyme-linked immune sorbent assay and the model of skin abscess in nude mice. Real-time polymerase chain reaction was used to detect whether the expression of virulence-associated genes of S. aureu were changed cultured with fusidic acid. Findings: A total of 504 genes greater than a 2- fold or less than -2-fold change in expression of S. aureus effected by sub-inhibitory concentration fusidic acid, including 232 up-regulated genes and 272 down-regulated genes were found by transcriptome sequencing. Sub-inhibitory concentrations of fusidic acid significantly inhibited the expression of saeRS, agrA, hla, lukFS, and sbi of S. aureus, and also reduce the hemolysis activity and α-toxin production of S. aureus. In the nude mouse abscess model, the average abscess area of the group treated with were significantly less than that of the group untreated. Interpretation: Our results suggested that the sub-inhibitory concentrations of fusidic acid may reduce the virulence of S. aureus by down-regulating agr and saeRS to reduce virulence-associated genes expression, which will provide a theoretical basis for the clinical treatment of S. aureus infection. Funding Statement: This study was supported by the National Natural Science Foundation of China (80216111). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Animal studies were approved by the Institutional Animal Care and Use Committee. We confirmed that all animal care and methods were performed in accordance with the guidelines and regulations approved by the Administration of Affairs Concerning Experimental Animals in China.