Exploring resveratrol dimers as virulence blocking agents - Attenuation of type III secretion in Yersinia pseudotuberculosis and Pseudomonas aeruginosa

Sci Rep. 2020 Feb 7;10(1):2103. doi: 10.1038/s41598-020-58872-0.

Abstract

Bacterial infections continue to threaten humankind and the rapid spread of antibiotic resistant bacteria is alarming. Current antibiotics target essential bacterial processes and thereby apply a strong selective pressure on pathogenic and non-pathogenic bacteria alike. One alternative strategy is to block bacterial virulence systems that are essential for the ability to cause disease but not for general bacterial viability. We have previously show that the plant natural product (-)-hopeaphenol blocks the type III secretion system (T3SS) in the Gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa. (-)-Hopeaphenol is a resveratrol tetramer and in the present study we explore various resveratrol dimers, including partial structures of (-)-hopeaphenol, as T3SS inhibitors. To allow rapid and efficient assessment of T3SS inhibition in P. aeruginosa, we developed a new screening method by using a green fluorescent protein reporter under the control of the ExoS promoter. Using a panel of assays we showed that compounds with a benzofuran core structure i.e. viniferifuran, dehydroampelopsin B, anigopreissin A, dehydro-δ-viniferin and resveratrol-piceatannol hybrid displayed significant to moderate activities towards the T3SS in Y. pseudotuberculosis and P. aeruginosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Benzofurans / pharmacology
  • Drug Discovery
  • Flavonoids / pharmacology
  • Genes, Reporter / genetics
  • Green Fluorescent Proteins / genetics
  • Phenols
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / pathogenicity
  • Resveratrol / analogs & derivatives
  • Resveratrol / pharmacology*
  • Stilbenes / pharmacology
  • Type III Secretion Systems / antagonists & inhibitors*
  • Virulence / drug effects
  • Yersinia pseudotuberculosis / drug effects*
  • Yersinia pseudotuberculosis / pathogenicity

Substances

  • Anti-Bacterial Agents
  • Benzofurans
  • Flavonoids
  • Phenols
  • Stilbenes
  • Type III Secretion Systems
  • hopeaphenol
  • Green Fluorescent Proteins
  • ampelopsin
  • benzofuran
  • Resveratrol