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Staphylococcus aureus  relies on quorum sensing to exert virulence to establish and maintain infection. Prior research demonstrated the potent quorum sensing inhibition effects of “430D-F5”, a refined extract derived from the fruits of  Schinus terebinthifolia , a medicinal plant used for the traditional treatment of skin and soft tissue infections. We report the isolation and identification of three compounds from 430D-F5 that reduce virulence and abate dermonecrosis: 3-oxo-olean-12-en-28-oic acid ( 1 ), 3-oxotirucalla-7,24Z-dien-26-oic acid ( 2 ) and 3α-hydroxytirucalla-7,24 Z-dien-27-oic acid ( 3 ). Each compound inhibits all  S. aureus  accessory gene regulator ( agr ) alleles (IC 50  2–70 μM). Dose-dependent responses were also observed in  agr- regulated reporters for leucocidin A ( lukA , IC 50  0.4-25 μM) and glycerol ester hydrolase or lipase ( gehB , IC 50  1.5–25 μM). Surprisingly, dose-dependent activity against the nuclease reporter ( nuc ), which is under the control of the  sae  two-component system, was also observed (IC 50  0.4–12.5 μM). Compounds  1-3  exhibited little to no effect on the  agr- independent  mgrA P2  reporter (a constitutive promoter from the  mgrA  two-component system) and the esxA reporter (under control of  mgrA ). Compounds  1 - 3  inhibited δ-toxin production  in  vitro and reduced dermonecrosis in a murine  in vivo  model. This is the first report of triterpenoid acids with potent anti-virulence effects against  S. aureus .

Triterpenoid acids isolated from Schinus terebinthifolia fruits reduce Staphylococcus aureus virulence and abate dermonecrosis