Intra- and Inter- Species Communication in Bacteria

 描述（由申请人提供） 项目摘要本项目的总体目标是了解群体感应：细菌中细胞间的通讯过程。这项拟议中的研究将探索群体感应受体区分密切相关，细胞外信号分子，并利用它们的结构差异来调节信号活性（目的1）该研究将确定胞外化学物质编码的信息在内部传递并由弧菌Qrr小调控RNA解释以精确控制全球基因表达的机制计划支撑集体行为（目标2）。目的3是我们最近发现的一个新的群体感应系统，包括一个新的细胞外信号分子，一个新的细胞质受体，一个新的调节小RNA，及其17个靶基因。新的细胞外群体感应信号分子可能由宿主微生物群产生，并且这在霍乱弧菌感染期间是相关的。拟议的研究是多学科的，采用微生物学，遗传学，生物化学，结构生物学，化学，物理理论，进化，成像和工程。在最一般的水平上，这项工作将提供深入了解物种内和物种间的通信，人口水平的合作，以及信号转导和信息处理的网络原则。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的理解，以及这些信息一旦被转导到细胞中，是如何被传递到控制基因表达和最终行为的。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，可能导致针对使用群体感应控制毒性和生物膜形成的细菌的抗微生物药物的开发，并改善高价值天然产品的工业生产。与上一个项目期间一样，正在研究两种弧菌（霍乱弧菌和哈维氏弧菌），以深入了解密切相关的物种如何通过进化独特地优化其群体感应电路，以执行不同的生物学。

 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.