Swarming motility and the regulation of flagellar biosynthesis in Bacillus subtilis

枯草芽孢杆菌的集群运动和鞭毛生物合成的调控

• 批准号: 9898391
• 负责人: Daniel B Kearns
• 金额: $ 48.98万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9898391
• 关键词: Anabolism; Architecture; Bacillus subtilis; Bacteria; Basic Science; Biochemistry; Cell surface; Cells; Complex; Environment; Flagella; Goals; Gram-Positive Bacteria; Learning; Length; Location; Mediating; Microscopy; Octodon; Pathogenesis; Pattern; Peptidoglycan; Pilum; Positioning Attribute; Proteins; Proteolysis; Regulation; Resolution; Rod; Solid; Stimulus; Surface; System; Thick; Time; Update; Virulence; Work; cell envelope; cell growth; cell motility; forward genetics; nanomachine; response; self organization; spatiotemporal

ABSTRACT Many bacteria are motile by synthesizing corkscrew-like flagella which when rotated propel bacteria through the environment. Each bacterium synthesizes a species-specific number of flagella and inserts the flagella in a species-specific pattern on the cell surface. Flagella are complex nanomachines assembled from dozens of different proteins and how each bacterial species controls flagellar number and patterning is poorly- understood. Moreover, the number of flagella per cell increases when cells come into contact a solid surface to initiate a form of surface motility called swarming. The Kearns lab uses classical forward genetics, super- resolution microscopy, and biochemistry to study flagellar biosynthesis and swarming motility of the Gram positive bacterium Bacillus subtilis. The goals of the project are to understand flagellar biosynthesis in the context of growing cell architecture. First, we will determine how flagellar number is controlled by the poorly- understood master regulator of flagellar biosynthesis SwrA and a response regulator DegU. Second, we will explore how the surface contact response is transduced to inhibit the adaptor-mediated regulatory proteolysis of SwrA and increase flagellar number. Third, we will learn how the flagellar rod insertion through peptidoglycan occurs, and how rod length is controlled to match the thickness of peptidoglycan. Fourth, flagella are synthesized in a grid-like pattern and we will study how flagellar patterning is interpreted and updated in time during cell growth, and coordinated with peptidoglycan insertion. Ultimately, we want to achieve a holistic understanding of how a cell dynamically governs the initiation of flagellar biosynthesis at specific locations to insert the machine through the cell envelope. Our basic research is fundamental to how cells self-organize and is applicable to the spatiotemporal control of the assembly of transenvelope nanomachines involved in pathogenesis including flagella, pili and secretion systems like the injectisome.

摘要 许多细菌通过合成开瓶器状的鞭毛来移动，当旋转时，鞭毛推动细菌 通过环境。每个细菌合成特定于物种的鞭毛数量，并将 鞭毛在细胞表面形成物种特有的图案。鞭毛是复杂的纳米机器，由 几十种不同的蛋白质，以及每种细菌如何控制鞭毛的数量和模式是糟糕的- 明白了。此外，当细胞接触到固体表面时，每个细胞的鞭毛数量增加。 发起一种称为蜂群运动的表面运动。卡恩斯实验室使用经典的正向遗传学，超级- 分辨率显微镜和生化研究革兰氏菌鞭毛的生物合成和成群运动 阳性细菌枯草芽孢杆菌。该项目的目标是了解鞭毛的生物合成。 不断增长的单元架构的背景。首先，我们将确定鞭毛数量是如何由不好的- 了解鞭毛生物合成的主要调控因子SWRA和反应调节因子DECU。第二，我们将 探索表面接触反应如何被转导以抑制接头介导的调节性蛋白降解 增加鞭毛数。第三，我们将学习鞭毛杆是如何通过 肽聚糖的产生，以及如何控制杆长以匹配肽聚糖的厚度。第四，鞭毛 是以网格状图案合成的，我们将研究鞭毛图案是如何在 细胞生长过程中的时间，并与肽聚糖插入相协调。最终，我们希望实现全面的 了解细胞如何动态地控制特定位置鞭毛生物合成的启动 将机器插入电池信封。我们的基础研究是细胞如何自组织和 适用于跨包络纳米机器组装的时空控制 发病机制包括鞭毛、菌毛和类似注射剂的分泌系统。