Castanea sativa (European Chestnut) Leaf Extracts Rich in Ursene and Oleanene Derivatives Block Staphylococcus aureus Virulence and Pathogenesis without Detectable Resistance.
Castanea sativa (European Chestnut) Leaf Extracts Rich in Ursene and Oleanene Derivatives Block Staphylococcus aureus Virulence and Pathogenesis without Detectable Resistance.
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DOI：
10.1371/journal.pone.0136486
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Horswill AR
中科院分区：
文献类型：
--
作者：
Quave CL;Lyles JT;Kavanaugh JS;Nelson K;Parlet CP;Crosby HA;Heilmann KP;Horswill AR
地中海拥有丰富的医学传统历史，这些传统在数千年来不同文化的影响下发展起来。今天，许多这样的传统仍然活在当地人民的民间医疗实践中。对用于治疗皮肤和软组织感染的植物民间药物的调查使我们研究了板栗（欧洲板栗）的潜在抗菌活性。在这里，我们报告的群体感应抑制活性的精制和化学特征的欧洲板栗叶提取物，富含齐墩果烯和uraic衍生物（五环三萜），对所有金黄色葡萄球菌辅助基因调节（agr）等位基因。我们提出了agr阻断活性（IC 50 1.56-25 μg mL-1）的证据层，如毒素输出，报告基因测定溶血活性，细胞毒性研究和体内脓肿模型。我们证明了该提取物对人角质形成细胞和小鼠皮肤缺乏细胞毒性，也缺乏对S。金黄色葡萄球菌和一组皮肤标本。最后，我们证明了提取物的连续传代不会导致获得对群体淬灭组合物的抗性。总之，通过在没有生长抑制的情况下破坏群体感应，本研究提供了对非杀生物剂毒力抑制剂在未来抗生素治疗中可能发挥的作用的深入了解。
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.