Welsh Michael A, Blackwell Helen E
Department of Chemistry, University of Wisconsin-Madison, 1101 University Ave., Madison, WI 53706, USA.
Department of Chemistry, University of Wisconsin-Madison, 1101 University Ave., Madison, WI 53706, USA
FEMS Microbiol Rev. 2016 Sep;40(5):774-94. doi: 10.1093/femsre/fuw009. Epub 2016 Jun 5.
Bacteria can utilize chemical signals to coordinate the expression of group-beneficial behaviors in a method of cell-cell communication called quorum sensing (QS). The discovery that QS controls the production of virulence factors and biofilm formation in many common pathogens has driven an explosion of research aimed at both deepening our fundamental understanding of these regulatory networks and developing chemical agents that can attenuate QS signaling. The inherently chemical nature of QS makes studying these pathways with small molecule tools a complementary approach to traditional microbiology techniques. Indeed, chemical tools are beginning to yield new insights into QS regulation and provide novel strategies to inhibit QS. Here, we review the most recent advances in the development of chemical probes of QS systems in Gram-negative bacteria, with an emphasis on the opportunistic pathogen Pseudomonas aeruginosa We first describe reports of novel small molecule modulators of QS receptors and QS signal synthases. Next, in several case studies, we showcase how chemical tools have been deployed to reveal new knowledge of QS biology and outline lessons for how researchers might best target QS to combat bacterial virulence. To close, we detail the outstanding challenges in the field and suggest strategies to overcome these issues.
细菌能够利用化学信号，通过一种称为群体感应（QS）的细胞间通讯方式来协调群体有益行为的表达。群体感应控制许多常见病原体中致病因子的产生和生物膜形成这一发现，推动了大量研究的开展，这些研究旨在加深我们对这些调控网络的基本理解，并开发能够减弱群体感应信号传导的化学试剂。群体感应固有的化学性质使得利用小分子工具研究这些途径成为传统微生物学技术的一种补充方法。事实上，化学工具正开始为群体感应调控带来新的见解，并提供抑制群体感应的新策略。在此，我们综述革兰氏阴性菌群体感应系统化学探针开发的最新进展，重点关注机会致病菌铜绿假单胞菌。我们首先描述群体感应受体和群体感应信号合成酶新型小分子调节剂的报道。接下来，在几个案例研究中，我们展示了化学工具是如何被用于揭示群体感应生物学的新知识，并概述研究人员如何最好地靶向群体感应以对抗细菌毒力的经验教训。最后，我们详细阐述该领域面临的突出挑战，并提出克服这些问题的策略。
