Intra- and Inter- Species Communication in Bacteria

 描述(由申请人提供) 项目摘要该项目的总体目标是了解群体感应：细菌中细胞间通讯的过程。拟议的研究将探索群体感应受体区分密切相关的细胞外信号分子并利用它们的结构差异调节信号活动的精细能力(目标1)研究将定义编码在细胞外化学物质中的信息在内部传递和由弧菌QrR小调节RNA解释的机制，以精确控制支撑集体行为的全球基因表达程序(目标2)。目的3重点介绍我们最近发现的一个新的群体感应系统，它由一个新的胞外信号分子、一个新的细胞质受体、一个新的调控小RNA及其17个靶基因组成。新的胞外群体感应信号分子可能是由宿主微生物群产生的，这与霍乱弧菌感染有关。拟议的研究是多学科的，运用了微生物学、遗传学、生物化学、结构生物学、化学、物理理论、进化论、成像学和工程学。在最一般的层面上，这项工作将提供对物种内和物种间的交流、种群水平的合作以及信号转导和信息处理的网络原则的洞察。在更具体的层面上，这项研究将促进对群体感应受体如何准确检测、区分和解码细胞外小分子中包含的信息，以及这些信息一旦被传递到细胞内，如何传递以控制基因表达，并最终控制行为的理解。在实践层面上，我的团队的研究可能会导致控制群体感应的策略，可能导致针对细菌的抗微生物药物的开发，这些细菌利用群体感应来控制毒力和生物膜的形成，并改善高价值天然产品的工业生产。与前一个项目期一样，正在研究两个弧菌物种(霍乱弧菌和哈维氏弧菌)，使人们得以深入了解，通过进化，相关物种如何独特地优化其群体感应电路，以执行不同的生物学任务。

 DESCRIPTION (provided by applicant) PROJECT ABSTRACT The overall goal of this project is to understand quorum sensing: the process of cell-cell communication in bacteria. The proposed research will probe the exquisite capacity of quorum-sensing receptors to differentiate between closely related, extracellular signal molecules and to exploit their structural differences to regulate signaling activity (Aim 1) The research will define the mechanisms by which the information encoded in the extracellular chemicals is relayed internally and interpreted by the vibrio Qrr small regulatory RNAs to precisely control the global gene expression program underpinning collective behaviors (Aim 2). Aim 3 focuses on our recent discovery of a new quorum-sensing system consisting of a novel extracellular signal molecule, a new cytoplasmic receptor, a new regulatory small RNA, and its 17 target genes. The new extracellular quorum- sensing signal molecule is likely generated by the host microbiota and this is relevant during Vibrio cholerae infection. The proposed research is multidisciplinary, employing microbiology, genetics, biochemistry, structural biology, chemistry, physics theory, evolution, imaging, and engineering. At the most general level, the work will provide insight into intra- and inter-species communication, population-level cooperation, and the network principles underlying signal transduction and information processing. At a more specific level, the research will advance understanding of how quorum-sensing receptors accurately detect, distinguish between, and decode information contained in extracellular small molecules and how that information, once transduced into the cell, is conveyed to control gene expression, and ultimately behavior. At a practical level, my group's investigations could lead to strategies for controlling quorum sensing, potentially resulting in th development of anti- microbial drugs aimed at bacteria that use quorum sensing to control virulence and biofilm formation, and improved industrial production of high-value natural products. As in the previous project period, two vibrio species (Vibrio cholerae and Vibrio harveyi) are under study, providing insight into how closely related species have, through evolution, uniquely optimized their quorum-sensing circuits to perform distinct biology.