Kim Han-Shin, Lee Sang-Hoon, Byun Youngjoo, Park Hee-Deung
School of Civil, Environmental and Architectural Engineering, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-713, South Korea.
College of Pharmacy, Korea University, Sejong-ro 2511, Jochiwon-eup, Sejong, 339-700, South Korea.
Sci Rep. 2015 Mar 2;5:8656. doi: 10.1038/srep08656.
Pseudomonas aeruginosa is a well-known pathogenic bacterium that forms biofilms and produces virulence factors via quorum sensing (QS). Interfering with normal QS interactions between signal molecules and their cognate receptors is a developing strategy for attenuating its virulence. Here we tested the hypothesis that 6-gingerol, a pungent oil of fresh ginger, reduces biofilm formation and virulence by antagonistically binding to P. aeruginosa QS receptors. In silico studies demonstrated molecular binding occurs between 6-gingerol and the QS receptor LasR through hydrogen bonding and hydrophobic interactions. Experimentally 6-gingerol reduced biofilm formation, several virulence factors (e.g., exoprotease, rhamnolipid, and pyocyanin), and mice mortality. Further transcriptome analyses demonstrated that 6-gingerol successfully repressed QS-induced genes, specifically those related to the production of virulence factors. These results strongly support our hypothesis and offer insight into the molecular mechanism that caused QS gene repression.
铜绿假单胞菌是一种著名的致病细菌，它通过群体感应（QS）形成生物膜并产生毒力因子。干扰信号分子与其同源受体之间的正常QS相互作用是一种减弱其毒力的新兴策略。在此，我们测试了一个假设，即新鲜生姜中的辛辣油6-姜酚通过与铜绿假单胞菌QS受体拮抗结合来减少生物膜形成和毒力。计算机模拟研究表明，6-姜酚与QS受体LasR之间通过氢键和疏水相互作用发生分子结合。实验表明，6-姜酚减少了生物膜形成、几种毒力因子（如外蛋白酶、鼠李糖脂和绿脓菌素）以及小鼠死亡率。进一步的转录组分析表明，6-姜酚成功抑制了QS诱导的基因，特别是那些与毒力因子产生相关的基因。这些结果有力地支持了我们的假设，并为导致QS基因抑制的分子机制提供了见解。
