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

• Type of Material: Article
• Authors: Huaqiao Tang, Emory University; Gina Porras, Emory University; Morgan M. Brown, University of Colorado; Francois Chassagne, Emory University; James T. Lyles, Emory University; John Bacsa, Emory University; Alexander R. Horswill, University of Colorado; Cassandra Quave, Emory University
• Language: English
• Date: 2020-05-15
• Publisher: Nature Portfolio
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-020-65080-3
• Title of Journal or Parent Work: Scientific Reports
• Volume: 10
• Issue: 1
• Start Page: 8046
• End Page: 8046
• Grant/Funding Information: ARH was supported by NIH grant AI133089 from the National Institute of Allergy and Infectious Diseases.; CLQ was supported by Emory University development funds.; We acknowledge the use of the Rigaku Synergy-S diffractometer, supported by the National Science Foundation under grant CHE-1626172.
• Keywords: Extraction; Colonization; AGR; In-vitro; Antioxidant; Bacterial biofilms; Multidisciplinary Sciences; Inhibitors; Science & Technology; Essential oil; Skin; Science & Technology - Other Topics

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.