Subinhibitory concentrations of resveratrol reduce alpha-hemolysin production in Staphylococcus aureus isolates by downregulating saeRS

Resveratrol is a natural phytoalexin. In recent studies, it has been shown to have beneficial effects on cardiovascular disease and cancer and has been deemed to have effective antiviral and immunomodulatory activities. Methicillin-resistant Staphylococcus aureus is a multidrug-resistant pathogen associated with skin and soft tissue infections. Alpha-hemolysin is known to play a key role in the symptoms caused by S. aureus, and the saeRS two-component system has been shown to be a major regulatory system of S. aureus virulence. The present study was designed to determine the effect of subinhibitory concentrations of resveratrol on the production of alpha-hemolysin in S. aureus. The effect of resveratrol on the transcription of S. aureus was studied by transcriptome sequencing. A total of 760 genes with >2-fold changes in expression were selected, including 479 upregulated genes and 281 downregulated genes. On the basis of transcriptome sequencing, the expression of alpha-hemolysin in the S. aureus strains of the resveratrol-treated group was downregulated. Our results showed that resveratrol weakly inhibited the growth of S. aureus strains, and subinhibitory concentration of resveratrol decreased the expression of hla and inhibited the regulation of saeRS. Hemolysis testing confirmed that resveratrol had an inhibitory effect on the hemolysis of rabbit erythrocytes infected with S. aureus strains in a dose-dependent manner. Resveratrol also decreased the hemolytic capacity by reducing the production of alpha-hemolysin. We found that resveratrol could decrease the expression of hla and reduce the secretion of alpha-hemolysin by downregulating saeRS. These findings have provided more evidence of the potential of resveratrol as a drug for resisting S. aureus infections.