Intra-and Inter Species Communication in Bacteria

细菌的种内和种间通讯

基本信息

批准号：
7252770
负责人：
BONNIE L BASSLER
金额：
$ 29.91万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-01 至 2011-06-30
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：我的研究的总体目标是了解法规传感：细菌中细胞 - 细胞通信过程。直到最近，细菌传达的能力才被认为是仅在几种海洋弧菌物种中发生的一种异常。现在很明显，细胞 - 细胞的通信是细菌世界中的常态，并且了解这一过程对于包括工业和临床微生物学在内的所有微生物学都是基础的，最终是了解较高生物体中的集体行为和发展。我们表明，沃尔里奥（Vibrio Cholerae）是欠发达国家的主要病原体，具有群体感应系统，并且该系统控制毒力。我们发现将多个法定感应信号引导到一个信号电路中。然而，该电路可以响应不同的信号输入，使差异基因表达。我们最近还发现，四个冗余的小调节RNA（SRNA）位于V.霍乱电路的核心，并且它们介导了群体感应开关，允许V.霍乱细胞从表现为个体的表现到作为坐标组的运作。因此，霍乱梭菌的群体感应电路已经表明自己非常适合探索有关如何在分子水平整合感觉信息的问题，以及如何通过多个提示控制的调节蛋白如何为这些输入提供差异响应提供机制。我们将研究V.霍乱，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V.霍乱来研究群体群体感应的分子开关，个人行为如何产生集体行为，并确定作为个人和作为协调社区成员的生存至关重要的基因。以上问题是本研究应用程序的重点。在最一般的层面上，这些研究将洞悉特征间和种间交流，人口级合作以及在细胞级别的信号转导和信息处理的网络原理。在更具体的水平上，这些研究将提高我们对SRNA介导的基因表达控制机制的理解，其全球性质一直不足以欣赏和在细菌中的研究不足。最后，在实际层面上，这些研究可能会导致控制法定感测的合成策略。目的包括开发针对使用法定人类感测来控制毒力的细菌的抗菌药物，以及改善天然产物（例如抗生素）的工业生产。