Intra- and Inter- Species Communication in Bacteria

细菌的种内和种间通讯

基本信息

批准号：
9221339
负责人：
BONNIE L BASSLER
金额：
$ 33.46万
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 2020-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9221339
关键词：
Affect Agonist Amino Acids Bacteria Base Pairing Behavior Binding Biochemical Biochemistry Biological Assay Biology Bioluminescence Catabolism Cell Communication Cell Density Cell Separation Cell physiology Cells Chemicals Chemistry Cholera Communication Communities Cues Cytoplasmic Receptors Detection Development Disease Dissection Engineering Evolution Fluorescence Gene Expression Gene Targeting Genetic Goals High-Throughput Nucleotide Sequencing Image Individual Industrialization Infection Information Theory Investigation Lead Ligands Maps Mass Spectrum Analysis Measures Mediating Membrane Messenger RNA Methods Microbial Biofilms Microbiology Microscopy Modeling Mucins Mus Mutagenesis Mutation Natural Products Nucleotides Organism Pathogenicity Phosphoric Monoester Hydrolases Physics Play Population Process Production RNA Regulation Research Role Signal Transduction Signaling Molecule Small RNA Specificity Structure System Transmembrane Domain Vibrio Vibrio cholerae Virulence Virulence Factors Work antimicrobial drug base chemical genetics chemical synthesis experimental study extracellular high throughput screening improved in vivo information processing insight metabolomics microbiota mouse model multidisciplinary mutant novel pathogen programs public health relevance quorum sensing receptor receptor binding response sensor histidine kinase small molecule stem structural biology theories

项目摘要

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.

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。拟议的研究将探讨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精湛能力。调节信号活动的结构差异（目标 1）该研究将确定细胞外化学物质编码的信息在内部传递并由弧菌 Qrr 小调节 RNA 解释以精确控制全局基因表达的机制支持集体行为的计划（目标 3）重点关注我们最近发现的一种新的群体感应系统，该系统由一种新的细胞外信号分子、一种新的细胞质受体、一种新的调节性小 RNA 及其 17 个新的靶基因组成。细胞外群体感应信号分子可能是由宿主微生物群产生的，这与霍乱弧菌感染期间相关。拟议的研究是多学科的，采用了微生物学、遗传学、在最一般的层面上，这项工作将提供对生物化学、结构生物学、化学、物理理论、进化、成像和工程学的见解，深入了解物种内和物种间的交流、群体水平的合作以及信号转导和基础的网络原理。在更具体的层面上，该研究将加深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转导到细胞中如何传递到控制基因的理解。表达，以及在实际层面上，我的团队的研究可能会导致控制群体感应的策略，从而可能导致开发针对利用群体感应来控制毒力和生物膜形成的细菌的抗微生物药物，并改善高浓度细菌的工业生产。 - 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它们的特性。群体感应电路来执行不同的生物学。