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: 7114995
• 负责人: ALAN D GROSSMAN
• 金额: $ 34.75万
• 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 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114995
• 关键词: Bacillus subtilis; bacterial genetics; bacterial proteins; binding sites; biological signal transduction; cell cell interaction; gene environment interaction; gene expression; genetic regulation; microarray technology; microorganism population study; phosphorylation; protein signal sequence; transcription factor; transposon /insertion element

DESCRIPTION (provided by applicant): Cell-cell signaling controls many processes in the biological world, including development, pathogenesis, growth, 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 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 Bacillus subtilis modulates gene expression and development in response to environmental conditions, with particular focus on aspects of peptide and cell-cell signaling. The major pathway for quorum sensing in B. subtilis involves activation of the transcription factor ComA, a response regulator that is active when phosphorylated. The activity of ComA is modulated by at least two different peptide signaling molecules that accumulate in culture supernatant as cells grow to high population density. A major challenge is to elucidate the range of cellular processes that are controlled by cell-cell signaling in a single species. This includes characterizing the genes that are regulated in response to population density, identifying the signaling molecules and pathways, and characterizing the web of overlapping interactions between responses to population density and other physiological signals. We will investigate these issues by characterizing the ComA-dependent quorum response, by characterizing other genes that are likely to be involved in cell-cell signaling, and by testing directly for and characterizing additional cell density-regulated responses. Central to this project is the use of DNA microarrays to characterize mRNA levels under a variety of conditions and in a variety of mutants. Our studies on quorum sensing and gene expression in B. subtilis, are relatively simple, experimentally accessible microbe should provide insights into general mechanisms of cell-cell signaling, signal transduction, and regulation.

描述(申请人提供)：细胞-细胞信号控制着生物世界中的许多过程，包括发育、发病、生长、交配和转化。信号传递过程通常是由一些细胞产生并被另一些细胞感知的因子(如激素、信息素、神经递质)介导的。在细菌中，感知和响应高种群密度的能力是一种细胞-细胞信号，通常被称为群体感应。细胞产生细胞外信号分子，随着种群密度的增加而积累，生理反应发生在临界密度。该项目的长期目标是了解枯草芽孢杆菌如何在环境条件下调节基因表达和发育，特别是在多肽和细胞-细胞信号转导方面。枯草杆菌群体感应的主要途径涉及转录因子COMA的激活，这是一种反应调节因子，在磷酸化时是活跃的。COM的活性受至少两个不同的肽信号分子的调节，当细胞生长到高密度时，这两个分子在培养上清液中积累。一个主要的挑战是阐明在单个物种中由细胞-细胞信号控制的细胞过程的范围。这包括确定受种群密度调控的基因的特征，确定信号分子和通路，以及描述对种群密度和其他生理信号的反应之间重叠相互作用的网络。我们将通过表征昏迷依赖的群体反应，通过表征其他可能参与细胞-细胞信号传递的基因，以及通过直接测试和表征额外的细胞密度调节反应来研究这些问题。这个项目的核心是使用DNA微阵列来表征各种条件下和各种突变体中的mRNA水平。我们对枯草杆菌群体感应和基因表达的研究相对简单，实验上可获得的微生物应该为深入了解细胞-细胞信号、信号转导和调控的一般机制提供见解。