QUORUM SENSING AND GENE EXPRESSION IN BACILLUS SUBTILIS

枯草芽孢杆菌中的群体感应和基因表达

• 批准号: 6180251
• 负责人: ALAN D GROSSMAN
• 金额: $ 31.11万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6180251
• 关键词: Bacillus subtilis; bacterial genetics; bacterial proteins; biological signal transduction; cell cycle; gene expression; genetic regulation; genetic regulatory element; molecular cloning; pheromone; protein biosynthesis; protein purification; protein structure function; site directed mutagenesis

DESCRIPTION: Cell-cell signaling controls many processes in the biological world, including development, pathogenesis, mating, and transformation. Signaling processes are often mediated by factors (e. g., hormones, pheromones, neurotransmitters) that are produced by some cells and sensed by others. In bacteria, the ability to sense and respond to high population density is a type of autocrine cell-cell signaling often referred to as quorum sensing. Cells produce extracellular signaling molecules that accumulate as population density increases, and a physiological response occurs at a critical density. The long term goal of this project is to understand how quorum sensing controls gene expression and differentiation in Bacillus subtilis. We will focus on two peptide signaling factors that contribute to quorum sensing in B. subtilis: (1) ComX pheromone, a 10 amino acid peptide with a hydrophobic modification on a tryptophan, and (2) competence and sporulation stimulating factor, CSF, an unmodified pentapeptide. Both signaling molecules accumulate in culture medium as cells grow to high density and contribute to the activation (phosphorylation) of the transcription factor ComA. There are many steps required for signaling by ComX pheromone and CSF, including production of the active signaling molecules and interaction with the appropriate target molecules. CSF is transported into the cell via a the oligopeptide permease Spo0K, a member of the large family of ATP-dependent transporters, whereas ComX pheromone probably interacts with a membrane receptor histidine protein kinase ComP. We plan to address the following questions relating to both ComX pheromone and CSF: What are the determinants of biological activity? What controls production? What are the mechanisms of the response and what are the direct targets of interaction? What genes are activated by the cellular response? Our studies on quorum sensing and gene expression in this relatively simple, experimentally accessible microbe should provide insights into general mechanisms of cell-cell signaling, signal transduction, and regulation.

描述：细胞-细胞信号控制着生物体内的许多过程。 世界，包括发育、发病、交配和转化。 信号传递过程通常由多种因素(例如，激素， 信息素、神经递质)，由某些细胞产生并由 其他。在细菌中，感知并对高种群作出反应的能力 密度是一种自分泌细胞-细胞信号，通常被称为 法定人数感应。细胞产生细胞外信号分子， 随着种群密度的增加而积累，以及一种生理反应 以临界密度发生。 该项目的长期目标是了解法定人数感知 控制枯草芽孢杆菌的基因表达和分化。我们会 关注与群体感应有关的两个多肽信号因子 枯草杆菌：(1)ComX信息素，一种10个氨基酸的疏水性多肽 色氨酸的修饰，以及(2)活性和产孢量刺激 因子，脑脊液，一种未经修饰的五肽。两个信号分子 随着细胞生长到高密度，在培养基中积累，并有助于 转录因子COMA的激活(磷酸化)。那里 ComX信息素和CSF是否需要许多步骤才能发出信号，包括 活性信号分子的产生及其与细胞的相互作用 合适的目标分子。脑脊液通过细胞内的 寡肽通透酶Spo0K，ATP依赖大家族的成员 转运体，而ComX信息素可能与膜相互作用 受体组氨酸蛋白激酶复合体。我们计划解决以下问题 与ComX信息素和脑脊液有关的问题： 生物活性的决定因素？是什么控制着生产？何谓 反应的机制和什么是直接的目标 互动？细胞反应激活了哪些基因？我们的 这种相对简单的群体感应和基因表达的研究， 可通过实验获得的微生物应该提供对一般情况的洞察 细胞-细胞信号、信号转导和调节的机制。