Castanea sativa (European Chestnut) Leaf Extracts Rich in Ursene and Oleanene Derivatives Block Staphylococcus aureus Virulence and Pathogenesis without Detectable Resistance

PLoS One. 2015 Aug 21;10(8):e0136486. doi: 10.1371/journal.pone.0136486. eCollection 2015.


The Mediterranean is home to a rich history of medical traditions that have developed under the influence of diverse cultures over millennia. Today, many such traditions are still alive in the folk medical practices of local people. Investigation of botanical folk medicines used in the treatment of skin and soft tissue infections led us to study Castanea sativa (European Chestnut) for its potential antibacterial activity. Here, we report the quorum sensing inhibitory activity of refined and chemically characterized European Chestnut leaf extracts, rich in oleanene and ursene derivatives (pentacyclic triterpenes), against all Staphylococcus aureus accessory gene regulator (agr) alleles. We present layers of evidence of agr blocking activity (IC50 1.56-25 μg mL-1), as measured in toxin outputs, reporter assays hemolytic activity, cytotoxicity studies, and an in vivo abscess model. We demonstrate the extract's lack of cytotoxicity to human keratinocytes and murine skin, as well as lack of growth inhibitory activity against S. aureus and a panel of skin commensals. Lastly, we demonstrate that serial passaging of the extract does not result in acquisition of resistance to the quorum quenching composition. In conclusion, through disruption of quorum sensing in the absence of growth inhibition, this study provides insight into the role that non-biocide inhibitors of virulence may play in future antibiotic therapies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacterial Toxins / antagonists & inhibitors
  • Bacterial Toxins / biosynthesis
  • Cell Line
  • Cells, Cultured
  • Drug Resistance, Bacterial
  • Erythrocytes / cytology
  • Erythrocytes / drug effects
  • Fagaceae / chemistry*
  • Hemolysin Proteins / antagonists & inhibitors
  • Hemolysin Proteins / biosynthesis
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Mice
  • Microbial Sensitivity Tests
  • Oleanolic Acid / isolation & purification
  • Oleanolic Acid / pharmacology*
  • Plant Extracts / chemistry
  • Plant Leaves / chemistry
  • Quorum Sensing / drug effects*
  • Rabbits
  • Staphylococcal Skin Infections / drug therapy*
  • Staphylococcal Skin Infections / microbiology
  • Staphylococcal Skin Infections / pathology
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / pathogenicity
  • Trans-Activators / antagonists & inhibitors*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Virulence / drug effects


  • Agr protein, Staphylococcus aureus
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Bacterial Toxins
  • Hemolysin Proteins
  • Plant Extracts
  • Trans-Activators
  • staphylococcal alpha-toxin
  • staphylococcal delta toxin
  • Oleanolic Acid