Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706-1322, USA.
J Org Chem. 2010 Oct 15;75(20):6737-46. doi: 10.1021/jo101237e.
Bacteria use small molecule signals to access their local population densities in a process called quorum sensing (QS). Once a threshold signal concentration is reached, and therefore a certain number of bacteria have assembled, bacteria use QS to change gene expression levels and initiate behaviors that benefit the group. These group processes play central roles in both bacterial virulence and symbiosis and can have significant impacts on human health, agriculture, and the environment. The dependence of QS on small molecule signals has inspired organic chemists to design non-native molecules that can intercept these signals and thereby perturb bacterial group behaviors. The opportunistic pathogen Pseudomonas aeruginosa has been the target of many of these efforts due to its prevalence in human infections. P. aeruginosa uses at least two N-acyl l-homoserine lactone signals and three homologous LuxR-type receptors to initiate a range of pathogenic behaviors at high cell densities, including biofilm formation and the production of an arsenal of virulence factors. This perspective highlights recent chemical efforts to modulate LuxR-type receptor activity in P. aeruginosa and offers insight into the development of receptor-specific ligands as potential antivirulence strategies.
细菌利用小分子信号来感知其在局部的种群密度，这个过程被称为群体感应（QS）。一旦达到一定的信号浓度阈值，也就是说有一定数量的细菌聚集在一起，细菌就会利用 QS 来改变基因表达水平，并启动有利于群体的行为。这些群体过程在细菌的毒力和共生中起着核心作用，并且会对人类健康、农业和环境产生重大影响。QS 对小分子信号的依赖激发了有机化学家设计非天然分子来截获这些信号，从而干扰细菌的群体行为。机会致病菌铜绿假单胞菌由于其在人类感染中的普遍性而成为这些努力的目标。铜绿假单胞菌至少使用两种 N-酰基高丝氨酸内酯信号和三种同源的 LuxR 型受体，在高细胞密度下启动一系列致病行为，包括生物膜形成和产生大量毒力因子。本综述重点介绍了近期在调节铜绿假单胞菌中 LuxR 型受体活性方面的化学研究进展，并为开发受体特异性配体作为潜在的抗毒力策略提供了新的思路。
