Umeå Centre for Microbial Research, Laboratories for Infection Medicine Sweden, Department of Chemistry, Umeå University, Umeå, Sweden.
PLoS One. 2013 Dec 4;8(12):e81969. doi: 10.1371/journal.pone.0081969. eCollection 2013.
Society faces huge challenges, as a large number of bacteria have developed resistance towards many or all of the antibiotics currently available. Novel strategies that can help solve this problem are urgently needed. One such strategy is to target bacterial virulence, the ability to cause disease e.g., by inhibition of type III secretion systems (T3SSs) utilized by many clinically relevant gram-negative pathogens. Many of the antibiotics used today originate from natural sources. In contrast, most virulence-blocking compounds towards the T3SS identified so far are small organic molecules. A recent high-throughput screening of a prefractionated natural product library identified the resveratrol tetramer (-)-hopeaphenol as an inhibitor of the T3SS in Yersinia pseudotuberculosis. In this study we have investigated the virulence blocking properties of (-)-hopeaphenol in three different gram-negative bacteria. (-)-Hopeaphenol was found to have micromolar activity towards the T3SSs in Yersinia pseudotuberculosis and Pseudomonas aeruginosa in cell-based infection models. In addition (-)-hopeaphenol reduced cell entry and subsequent intracellular growth of Chlamydia trachomatis.
社会面临着巨大的挑战，因为大量细菌对目前可用的许多或所有抗生素都产生了耐药性。急需寻找新的策略来解决这个问题。一种这样的策略是针对细菌的毒力，即引起疾病的能力，例如通过抑制许多临床相关的革兰氏阴性病原体利用的 III 型分泌系统（T3SS）。目前使用的许多抗生素都来源于天然来源。相比之下，迄今为止发现的针对 T3SS 的大多数毒力阻断化合物都是小分子有机化合物。最近对预分级天然产物文库进行高通量筛选，鉴定出白藜芦醇四聚体（-）-白藜芦醇酚是假结核耶尔森氏菌 T3SS 的抑制剂。在这项研究中，我们研究了（-）-白藜芦醇酚在三种不同的革兰氏阴性菌中的毒力阻断特性。在基于细胞的感染模型中，（-）-白藜芦醇酚对假结核耶尔森氏菌和铜绿假单胞菌的 T3SS 具有微摩尔活性。此外，（-）-白藜芦醇酚还减少了沙眼衣原体的细胞进入和随后的细胞内生长。
