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）：我研究的总体目标是了解群体感应：细菌中细胞间通讯的过程。直到最近，细菌的交流能力还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，细胞间通讯是细菌世界的常态，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，并最终了解高等生物体的集体行为和发育。我们发现，欠发达国家的主要病原体霍乱弧菌具有群体感应系统，并且该系统控制毒力。我们发现多个群体感应信号被引导到一个信号电路中；然而，该电路能够响应不同的信号输入而实现差异基因表达。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，使霍乱弧菌细胞从个体转变为协调群体。因此，霍乱弧菌群体感应电路非常适合探索如何在分子水平上整合感觉信息以及如何通过多种线索控制的调节蛋白提供对这些输入的差异反应的机制。。我们将研究霍乱弧菌，以了解 sRNA 调节行为的机制，并发现 sRNA 调节因子（相对于 DNA 结合蛋白）提供的独特控制特征。最后，我们将使用霍乱弧菌来检查群体感应的分子开关，个体行为如何引起集体行为，并确定对于个体和协调社区成员的生存至关重要的基因。上述问题是本研究应用的重点。在最一般的层面上，这些研究将深入了解物种内和物种间的交流、群体层面的合作，以及细胞层面信号转导和信息处理的网络原理。在更具体的层面上，这些研究将增进我们对 sRNA 介导的基因表达控制机制的理解，直到最近，其在细菌中的整体性质一直未被充分认识和研究。最后，在实践层面上，这些研究可能会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来控制毒力的细菌的抗微生物药物，以及改进抗生素等天然产物的工业生产。