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

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

Author information

1
Center for the Study of Human Health, Emory University, Atlanta, Georgia, United States of America; Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
2
Center for the Study of Human Health, Emory University, Atlanta, Georgia, United States of America.
3
Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
4
Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia, United States of America.

Abstract

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.

PMID:
26295163
PMCID:
PMC4546677
DOI:
10.1371/journal.pone.0136486
[Indexed for MEDLINE]
Free PMC Article

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