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: 6491613
• 负责人: ALAN D GROSSMAN
• 金额: $ 7.58万
• 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 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6491613
• 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：细胞间信号传导控制着生物体内的许多过程。 世界，包括发育、发病机制、交配和转化。 信号传导过程通常由因素介导（例如激素、 信息素、神经递质）由某些细胞产生并被 其他的。 在细菌中，感知和响应大量群体的能力 密度是一种自分泌细胞间信号传导，通常称为 群体感应。 细胞产生细胞外信号分子 随着人口密度的增加而积累，并产生生理反应 发生在临界密度。 该项目的长期目标是了解群体感应如何 控制枯草芽孢杆菌的基因表达和分化。 我们将 重点关注有助于群体感应的两种肽信号传导因子 B. subtilis：(1) ComX 信息素，一种具有疏水性的 10 个氨基酸肽 色氨酸修饰，以及 (2) 能力和孢子形成刺激 因子，CSF，一种未修饰的五肽。 两种信号分子 当细胞生长到高密度时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 发出信号需要许多步骤，包括 活性信号分子的产生以及与 合适的目标分子。 CSF 通过 寡肽通透酶 Spo0K，ATP 依赖性大家族的成员 转运蛋白，而 ComX 信息素可能与膜相互作用 受体组氨酸蛋白激酶 ComP。 我们计划解决以下问题 与 ComX 信息素和 CSF 相关的问题： 生物活性的决定因素？ 什么控制生产？ 什么是 应对机制以及直接目标是什么 相互作用？ 哪些基因被细胞反应激活？ 我们的 群体感应和基因表达的研究相对简单， 实验上可获取的微生物应该提供对一般情况的见解 细胞间信号传导、信号转导和调节的机制。