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（由申请人提供）：细胞间信号传导控制生物界的许多过程，包括发育、发病机制、生长、交配和转化。信号传导过程通常由一些细胞产生并被其他细胞感知的因素（例如激素、信息素、神经递质）介导。在细菌中，感知和响应高群体密度的能力是一种细胞间信号传导，通常称为群体感应。细胞产生细胞外信号分子，这些信号分子随着群体密度的增加而积累，并且在临界密度时发生生理反应。该项目的长期目标是了解枯草芽孢杆菌如何调节基因表达和发育以响应环境条件，特别关注肽和细胞间信号传导方面。枯草芽孢杆菌中群体感应的主要途径涉及转录因子 ComA 的激活，ComA 是一种在磷酸化时处于活动状态的反应调节因子。 ComA 的活性受到至少两种不同的肽信号分子的调节，当细胞生长到高群体密度时，这些信号分子会在培养物上清液中积累。一个主要的挑战是阐明单个物种中由细胞间信号传导控制的细胞过程的范围。这包括表征根据人口密度而调节的基因，识别信号分子和途径，以及表征对人口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 ComA 依赖性群体反应、表征可能参与细胞间信号传导的其他基因以及直接测试和表征其他细胞密度调节反应来研究这些问题。该项目的核心是使用 DNA 微阵列来表征各种条件下和各种突变体中的 mRNA 水平。我们对枯草芽孢杆菌群体感应和基因表达的研究是相对简单的、可通过实验获得的微生物，应该可以深入了解细胞间信号传导、信号转导和调节的一般机制。