Jiang Tianyu, Zhu Peng, Du Lupei, Li Minyong
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology of Natural Products (MOE), School of Pharmacy, Shandong University, 44 West Wenhua Road, Jinan, Shandong, 250012, China.
Methods Mol Biol. 2018;1673:353-362. doi: 10.1007/978-1-4939-7309-5_26.
Quorum sensing (QS) is a cell-to-cell communication system that regulates gene expression as a result of the production and perception of signal molecules called autoinducers (AIs). AI-2 is a QS autoinducer produced by both Gram-negative and Gram-positive bacteria, in which it regulates intraspecies and interspecies communication. The identification of QS inhibitors is considered a promising strategy for the development of anti-virulence drugs with reduced selective pressure for resistance. Here we describe a high-throughput virtual screening approach to identify AI-2 quorum sensing inhibitors on the basis of Vibrio harveyi LuxPQ crystal structure. Seven potent inhibitors with IC values in the micromolar range were selected with no effect or low effect on V. harveyi growth rate.
群体感应（QS）是一种细胞间通讯系统，它通过产生和感知称为自诱导物（AIs）的信号分子来调节基因表达。AI-2是一种由革兰氏阴性菌和革兰氏阳性菌产生的群体感应自诱导物，在这些细菌中它调节种内和种间通讯。群体感应抑制剂的鉴定被认为是开发抗毒力药物的一种有前景的策略，这种药物对耐药性的选择性压力较小。在这里，我们描述了一种基于哈维氏弧菌LuxPQ晶体结构的高通量虚拟筛选方法，以鉴定AI-2群体感应抑制剂。我们选择了七种IC值在微摩尔范围内的强效抑制剂，它们对哈维氏弧菌的生长速率没有影响或影响很小。
