Anti-infective activity of Salviae miltiorrhizae against Staphylococcus aureus by attenuating accessory gene regulator system-mediated virulence

For the reason of rapid evolution of antibiotic resistance in Staphylococcus aureus, antivirulence therapy may be a promising alternative for effective control of spread of resistant pathogens. The Chinese Materia Medica has been widely used for treatment of disease and production of health food, and it remains a valuable resource for discovery of compounds possessing antivirule nce activity.Through a Caenorhabditis elegans infection model, EtOAc-soluble fraction of 80% EtOH extract of Salvia miltiorrhiza Bunge (SMEA) was found to possess potential anti-infective activity against S. aureus. Then, several in vitro assays indicated that SMEA had robust antivirulence activity at the dose of 400 μg/mL, reducing hemolytic activity and α-hemolysin expression in S. aureus. Furthermore, at 100 mg/kg, SMEA reduced abscess formation in the main organs of mice challenged with S. aureus. In order to identify the bioactive components of SMEA and investigate the mechanisms underlying the antivirulence activity, SMEA was separated using bioassay-guided fractionation. As a result, eight compounds were identified in SMEA. Among them, tanshinone IIB (TNB) showed strong antivirulence activity both in vitro and in vivo. Furthermore, at 24 μg/mL, TNB significantly reduced the expression of RNAIII and psmα, indicating that the mechanism underlying TNB activity was related to the accessory gene regulator quorum sensing system. Collectively, the antivirulence effect of TNB making it a promising candidate for the development of drugs used against S. aureus infections.