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.

抽象的 许多细菌通过合成螺旋状鞭毛来运动，鞭毛旋转时会推动细菌 通过环境。每种细菌都会合成特定数量的鞭毛并插入 鞭毛在细胞表面上以物种特异性模式排列。鞭毛是复杂的纳米机器，由 数十种不同的蛋白质以及每种细菌如何控制鞭毛数量和模式尚不清楚- 明白了。此外，当细胞接触固体表面时，每个细胞的鞭毛数量会增加 启动一种称为蜂群的表面运动形式。卡恩斯实验室使用经典的正向遗传学，超 分辨率显微镜和生物化学研究革兰氏菌的鞭毛生物合成和集群运动 阳性菌为枯草芽孢杆菌。该项目的目标是了解鞭毛生物合成 生长细胞结构的背景。首先，我们将确定鞭毛数量是如何被不良控制的—— 了解鞭毛生物合成的主调节器 SwrA 和反应调节器 DegU。其次，我们将 探索表面接触反应如何转导以抑制接头介导的调节性蛋白水解 SwrA 并增加鞭毛数量。第三，我们将了解鞭毛杆如何插入 肽聚糖的发生，以及如何控制杆长度以匹配肽聚糖的厚度。四、鞭毛 以网格状图案合成，我们将研究如何解释和更新鞭毛图案 细胞生长期间的时间，并与肽聚糖插入相协调。最终，我们希望实现一个整体的 了解细胞如何动态控制特定位置鞭毛生物合成的启动 将机器插入电池外壳。我们的基础研究对于细胞如何自组织和 适用于涉及跨包膜纳米机器组装的时空控制 发病机制包括鞭毛、菌毛和注射系统等分泌系统。