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

ABSTRACT: 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 3?-hydroxytirucalla-7,24 Z-dien-27-oic acid (3). Each compound inhibits all S. aureus accessory gene regulator (agr) alleles (IC₅₀ 2-70??M). Dose-dependent responses were also observed in agr-regulated reporters for leucocidin A (lukA, IC₅₀ 0.4-25??M) and glycerol ester hydrolase or lipase (gehB, IC₅₀ 1.5-25??M). Surprisingly, dose-dependent activity against the nuclease reporter (nuc), which is under the control of the sae two-component system, was also observed (IC₅₀ 0.4-12.5??M). 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 ?-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.

SUBMITTER: Tang H 

PROVIDER: S-EPMC7229044 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature