Intercellular Signalling in Vibrio harveyi

本研究的长期目标是探索细菌用于细胞间通讯的分子机制。本项目主要研究海洋生物发光模式细菌哈维弧菌的群体感应。已经证明，V. harveyi有两个群体感应电路（信号系统1和信号系统2），它们汇聚在一起调节光产生（Lux）。每个系统由双组件传感器-自动感应对组成：LuxN/AI-1用于系统1，LuxPQ/AI-2用于系统2。两个传感器都将信息传递给一个共享的磷接力蛋白LuxU，后者再将信号传递给响应调节蛋白LuxO。Phospho-LuxO间接负责在低细胞密度下抑制荧光素酶的产生，因为它激活了Lux负调节因子的表达。转录激活蛋白LuxR也是荧光素酶结构操纵子（luxCDABEGH）表达所必需的。结果表明，哈维依利用信号系统1和AI-1进行种内通信，利用信号系统2和AI-2进行种间通信。许多细菌，包括一些临床上重要的病原体都会产生AI-2。本项目的目标是鉴定和表征V. harveyi多通道群体感应信号通路的组分，确定不同信号蛋白的功能和相互作用，并确定两个系统的信号整合机制。对这一调控网络的分析将导致对细菌如何整合、处理和转导感觉信息以控制基因表达以响应细胞间通信的分子理解。对这个电路的分析对于理解细菌如何感知和对环境做出反应，它们如何与彼此以及与其他种类的细菌交流，以及它们如何构建复杂的群落结构是有价值的。由于调控过程复杂，涉及细胞内、细胞间、种内和种间的信号传递，可能会揭示有趣的新机制。

The long term goal of this research is to explore the molecular mechanisms that bacteria use for inter-cellular communication. This project focuses on a study of quorum sensing in the model bioluminescent marine bacterium Vibrio harveyi. It has been demonstrated that V. harveyi has two quorum sensing circuits (Signaling System 1 and Signaling System 2) that converge to regulate light production (Lux). Each system is made up of a two-component sensor-auto-inducer pair: LuxN/AI-1 for System 1 and LuxPQ/AI-2 for System 2. Both sensors transduce information to a shared phosphorelay protein, LuxU, which in turn conveys the signal to the response regulator protein LuxO. Phospho-LuxO is indirectly responsible for repression of luciferase production at low cell density, because it activates the expression of a negative regulator of Lux. A transcriptional activator protein, LuxR, is also required for expression of the luciferase structural operon (luxCDABEGH). Results suggest that V. harveyi uses Signaling System 1 and AI-1 for intra-species communication and Signaling System 2 and AI-2 for inter-species communication. Many bacteria including a number of clinically important pathogens produce AI-2. The goal of this project is to identify and characterize components of the V. harveyi multi-channel quorum sensing signalling pathway, to determine the functions and interactions of the different signalling proteins, and to determine the mechanism of signal integration by the two systems. The analysis of this regulatory network will lead to a molecular understanding of how bacteria integrate, process and transduce sensory information to control gene expression in response to inter-cellular communication. Analysis of this circuit should be valuable for understanding how bacteria perceive and react to their environment, how they communicate with one another and with other species of bacteria, and how they architect elaborate community structures. Since the regulatory process is complex and involves intra-cellular, inter-cellular, intra-species and inter-species signal transmission, interesting new mechanisms could be revealed.