Intra-and Inter Species Communication in Bacteria

描述（由申请人提供）：我研究的总体目标是理解群体感应：细菌中细胞-细胞通信的过程。直到最近，细菌的交流能力被认为是一种异常现象，只发生在少数海洋弧菌物种中。现在很清楚，细胞间的交流是细菌世界的常态，理解这一过程是所有微生物学的基础，包括工业和临床微生物学，并最终理解高等生物的集体行为和发育。我们发现霍乱弧菌是欠发达国家的一种主要病原体，它有一个群体感应系统，这个系统控制着毒力。我们发现，多个群体感应信号被引入一个信号电路；然而，该电路能够对不同的信号输入作出不同的基因表达。我们最近还发现，四个冗余的小调控rna （sRNAs）位于霍乱弧菌回路的核心，它们介导群体感应开关，使霍乱弧菌细胞从作为个体转变为作为一个协调的群体。因此，霍乱弧菌群体感应回路显示出它非常适合探索以下问题：感觉信息是如何在分子水平上整合的，以及受多种信号控制的调节蛋白是如何对这些输入提供不同反应的机制的。我们将研究霍乱弧菌，以了解sRNA调节行为的机制，并发现sRNA调节剂提供的独特控制特征（与dna结合蛋白相反）。最后，我们将使用霍乱弧菌来研究群体感应的分子开关，个体行为如何引起集体行为，并确定作为个体和作为协调社区成员生存的关键基因。以上问题是本研究应用的重点。在最普遍的层面上，这些研究将为物种内和物种间的交流、种群水平的合作以及细胞水平上信号转导和信息处理的网络原理提供见解。在更具体的层面上，这些研究将促进我们对srna介导的基因表达控制机制的理解，直到最近，这种机制在细菌中的全球性质还没有得到充分的认识和研究。最后，在实际层面上，这些研究可能导致控制群体感应的综合策略。目标包括开发针对利用群体感应控制毒力的细菌的抗微生物药物，以及改善抗生素等天然产物的工业生产。

DESCRIPTION (provided by applicant): The overall goal of my research is to understand quorum sensing: the process of cell-cell communication in bacteria. Until recently, the ability of bacteria to communicate was considered an anomaly that occurred only in a few marine vibrio species. It is now clear that cell-cell communication is the norm in the bacterial world and that understanding this process is fundamental to all of microbiology, including industrial and clinical microbiology, and ultimately to understanding collective behaviors and development in higher organisms. We showed that Vibrio cholerae, a major pathogen in under-developed countries, has a quorum-sensing system and that this system controls virulence. We discovered that multiple quorum-sensing signals are channeled into one signaling circuit; yet the circuit enables differential gene expression in response to the different signal inputs. We also recently discovered that four redundant small regulatory RNAs (sRNAs) lie at the heart of the V. cholerae circuit, and that they mediate the quorum-sensing switch allowing V. cholerae cells to transition from acting as individuals to functioning as a coordinated group. Thus, the V. cholerae quorum- sensing circuit has revealed itself to be ideally suited for explorations of questions concerning how sensory information is integrated at the molecular level and how regulatory proteins controlled by multiple cues can nonetheless provide a mechanism for differential responses to those inputs. We will study V. cholerae to learn the mechanism by which sRNAs regulate behavior, and to discover the unique control features provided by sRNA regulators (as opposed to DNA-binding proteins). Finally, we will use V. cholerae to examine the molecular switch underlying quorum sensing, how individual behaviors give rise to collective behaviors, and to identify the genes that are critical for survival as an individual and as a member of a coordinated community. The above questions are the focus of this research application. At the most general level, these studies will provide insight into intra- and inter-species communication, population-level cooperation, and the network principles underlying signal transduction and information processing at the cellular level. At a more specific level, these studies will advance our understanding of the mechanisms of sRNA-mediated control of gene expression, the global nature of which has been, until recently, under- appreciated and under-studied in bacteria. Finally, at a practical level, these investigations could lead to synthetic strategies for controlling quorum sensing. Objectives include development of anti-microbial drugs aimed at bacteria that use quorum sensing to control virulence, and improved industrial production of natural products such as antibiotics.