Department of Chemistry, Umeå University, SE 901 87, Umeå, Sweden.
School of Science (Applied Chemistry and Environmental Science), RMIT University, GPO Box 2476 Melbourne, Victoria, 3001, Australia.
Sci Rep. 2020 Feb 7;10(1):2103. doi: 10.1038/s41598-020-58872-0.
Bacterial infections continue to threaten humankind and the rapid spread of antibiotic resistant bacteria is alarming. Current antibiotics target essential bacterial processes and thereby apply a strong selective pressure on pathogenic and non-pathogenic bacteria alike. One alternative strategy is to block bacterial virulence systems that are essential for the ability to cause disease but not for general bacterial viability. We have previously show that the plant natural product (-)-hopeaphenol blocks the type III secretion system (T3SS) in the Gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa. (-)-Hopeaphenol is a resveratrol tetramer and in the present study we explore various resveratrol dimers, including partial structures of (-)-hopeaphenol, as T3SS inhibitors. To allow rapid and efficient assessment of T3SS inhibition in P. aeruginosa, we developed a new screening method by using a green fluorescent protein reporter under the control of the ExoS promoter. Using a panel of assays we showed that compounds with a benzofuran core structure i.e. viniferifuran, dehydroampelopsin B, anigopreissin A, dehydro-δ-viniferin and resveratrol-piceatannol hybrid displayed significant to moderate activities towards the T3SS in Y. pseudotuberculosis and P. aeruginosa.
细菌感染继续威胁着人类，抗生素耐药菌的迅速传播令人震惊。目前的抗生素针对的是细菌的必需过程，因此对病原体和非病原体细菌都施加了强烈的选择压力。另一种策略是阻断细菌毒力系统，这些系统对于致病能力是必需的，但对于一般细菌的生存能力并非必需。我们之前已经表明，植物天然产物（-）-槐酚可阻断革兰氏阴性病原体假结核耶尔森氏菌和铜绿假单胞菌中的 III 型分泌系统（T3SS）。（-）-槐酚是白藜芦醇的四聚体，在本研究中，我们探索了各种白藜芦醇二聚体，包括（-）-槐酚的部分结构，作为 T3SS 抑制剂。为了允许在铜绿假单胞菌中快速有效地评估 T3SS 抑制作用，我们开发了一种新的筛选方法，使用 ExoS 启动子控制的绿色荧光蛋白报告基因。通过一系列测定，我们表明具有苯并呋喃核心结构的化合物，即二氢白藜芦醇、去氢ampelopsin B、阿尼戈普雷辛 A、去氢-δ-白藜芦醇和白藜芦醇-白皮杉醇杂种，对假结核耶尔森氏菌和铜绿假单胞菌的 T3SS 具有显著到中等的活性。
