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

Sci Rep. 2020 May 15;10(1):8046. doi: 10.1038/s41598-020-65080-3.

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 3α-hydroxytirucalla-7,24 Z-dien-27-oic acid (3). Each compound inhibits all S. aureus accessory gene regulator (agr) alleles (IC50 2-70 μM). Dose-dependent responses were also observed in agr-regulated reporters for leucocidin A (lukA, IC50 0.4-25 μM) and glycerol ester hydrolase or lipase (gehB, IC50 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 (IC50 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anacardiaceae / chemistry*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects
  • Dose-Response Relationship, Drug
  • Fruit / chemistry*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / pathogenicity
  • Triterpenes / chemistry
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology*
  • Virulence / drug effects

Substances

  • Anti-Bacterial Agents
  • Plant Extracts
  • Triterpenes