Forespore Engulfment During B subtilis Sporulation

枯草芽孢杆菌孢子形成过程中前孢子的吞噬

• 批准号: 8589593
• 负责人: Kit J Pogliano
• 金额: $ 37.7万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8589593
• 关键词: Adhesions; Anabolism; Anthrax disease; Antibiotics; Bacillus (bacterium); Bacillus subtilis; Bacteria; Biochemical; Biogenesis; Biological; Botulism; Burn injury; Cell Wall; Cell division; Cells; Cellular Structures; Chromosome Segregation; Clostridium; Clostridium botulinum; Complex; Cytolysis; Cytoplasm; Development; Drug Targeting; Electrons; Enzymes; Event; Genes; Genetic; Gram-Positive Bacteria; Immigration; Individual; Infectious Agent; Lighting; Mediating; Membrane; Membrane Fusion; Methods; Microscopy; Modeling; Mothers; Movement; Mutation; N-Acetylmuramoyl-L-alanine Amidase; Pathway interactions; Peptidoglycan; Phagocytosis; Photobleaching; Play; Positioning Attribute; Process; Production; Proteins; Recombinant Proteins; Regulation; Relative (related person); Reproduction spores; Resolution; Role; Speed; Staging; Structure; System; Testing; macromolecule; migration; mutant; novel; photoactivation; prevent; protein complex; protein protein interaction; public health relevance; research study

DESCRIPTION (provided by applicant): Bacteria from the genera Bacillus and Clostridium produce unusually durable endospores that are the infectious agent of Anthrax and Botulism. The phagocytosis-like process of engulfment is the hallmark of endospore formation, as it creates the unique cell within a cell structure that allows spore assembly to occur within the cytoplasm. However, it has remained unclear how bacterial cells evolved the ability to perform engulfment given the simplicity of their cellular machinery and the seemingly insurmountable barrier presented by the cell wall that surrounds bacterial cells. Our studies suggest that membrane migration during engulfment is mediated by one essential protein machinery, the SpoIID/SpoIIM/SpoIIP complex that degrades the bacterial cell wall, plus two partially redundant machineries, the SpoIIQ-SpoIIIAH complex that provides a zipper-like adhesion between the developing cells and peptidoglycan biosynthesis which is essential for membrane migration when SpoIIQ is absent. The final step of engulfment, membrane fission, requires both ongoing peptidoglycan biogenesis and SpoIIIE, which is also required for the final stages of chromosome segregation and septal membrane fission during the asymmetrically positioned cell division event of sporulation. We will take a combined cell biological, genetic and biochemical approach to study the spatial regulation of peptidoglycan degradation and synthesis, the protein-protein interactions that mediate engulfment, and to understand the mechanisms by which bacterial cells catalyze membrane fission and are dynamically organized. Engulfment provides a dispensable system to study cell biological events that are essential for all bacteria, such as protein localization and membrane fusion.

描述（由申请人提供）： 芽孢杆菌属和梭状芽孢杆菌属的细菌产生异常耐用的内生孢子，它们是炭疽和肉毒杆菌的传染源。类似吞噬作用的吞噬过程是内生孢子形成的标志，因为它在细胞结构内创建了独特的细胞，允许孢子在细胞质内组装。然而，鉴于细菌细胞机制的简单性以及细菌细胞周围细胞壁所呈现的看似不可逾越的屏障，细菌细胞如何进化出吞噬能力仍不清楚。我们的研究表明，吞噬过程中的膜迁移是由一种重要的蛋白质机制介导的，即降解细菌细胞壁的 SpoIID/SpoIIM/SpoIIP 复合物，以及两种部分冗余的机制，即 SpoIIQ-SpoIIIAH 复合物，该复合物在发育细胞和肽聚糖生物合成之间提供拉链状粘附，这对于 SpoIIQ 时的膜迁移至关重要 缺席。吞噬的最后一步，即膜裂变，需要正在进行的肽聚糖生物发生和 SpoIIIE，这也是孢子形成的不对称定位细胞分裂事件期间染色体分离和隔膜裂变的最后阶段所需要的。我们将采用细胞生物学、遗传和生化相结合的方法来研究肽聚糖降解和合成的空间调控、介导吞噬的蛋白质-蛋白质相互作用，并了解细菌细胞催化膜裂变和动态组织的机制。吞噬提供了一个可有可无的系统来研究对所有细菌都至关重要的细胞生物学事件，例如蛋白质定位和膜融合。