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.
Highlights
Alarming trends in the spread of antibiotic resistance among top pathogens, including Staphylococcus aureus, have placed mankind at the brink of what has been coined as the ‘post-PLOS ONE | DOI:10.1371/journal.pone.0136486 August 21, 2015Chestnut Extracts Block S. aureus Virulence and Pathogenesis
We continue to explore other mechanisms by which anti-infective traditional botanical medicines may function, and report the discovery of quorum quenching natural products extracted from Castanea sativa (European Chestnut) leaves, which are used in traditional therapies for treating skin inflammation soft tissue infections (SSTI) in the Mediterranean [7]
Growth inhibitory impact of the extracts was assessed with traditional static Minimum inhibitory concentration (MIC) assays (Table 2); growth inhibition was tracked in the fluorescent reporter assays for agr activity (Fig 3)
Summary
Alarming trends in the spread of antibiotic resistance among top pathogens, including Staphylococcus aureus, have placed mankind at the brink of what has been coined as the ‘post-. We continue to explore other mechanisms by which anti-infective traditional botanical medicines may function, and report the discovery of quorum quenching natural products extracted from Castanea sativa (European Chestnut) leaves, which are used in traditional therapies for treating skin inflammation SSTIs in the Mediterranean [7]. S. aureus produces an extensive array of enzymes, hemolysins, and toxins that are essential to its ability to spread through tissues and cause disease [9] These virulence factors serve a wide scope of purposes in the infection process, including disruption of the epithelial barrier, inhibition of opsonization by antibody and complement, neutrophil cytolysis, interference with neutrophil chemotaxis, and inactivation of antimicrobial peptides [10,11,12,13]. We hypothesize that by using a complex botanical composition to target quorum sensing rather than growth inhibition, the typical pitfalls of classical antibiotics can be avoided by limiting impact on the cutaneous microbiome and avoiding generation of resistance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
