Studies of Bacterial Endospore Germination

细菌内孢子萌发的研究

• 批准号: 10032962
• 负责人: DAVID L POPHAM
• 金额: $ 30.63万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-26 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10032962
• 关键词: Agriculture; Animal Diseases; Anthrax disease; Botulism; Cells; Cellular Structures; Colitis; Cytoplasmic Protein; Decontamination; Effectiveness; Elements; Environment; Enzymes; Event; Food; Food Poisoning; Gene Proteins; Genes; Genetic; Germination; Goals; Growth; Hour; Hydration status; Industrialization; Infection; Knowledge; Lead; Life; Lipids; Membrane; Membrane Fluidity; Membrane Proteins; Metabolic; Metabolism; Methods; Modification; Multiprotein Complexes; Organism; Pathogenesis; Peptide Hydrolases; Planet Earth; Play; Procedures; Process; Property; Protease Inhibitor; Proteins; Proteolysis; Reproduction spores; Resistance; Role; Structure; Surface; Tetanus; Work; base; gene discovery; human disease; improved; mutant; novel; physical assault; prevent; protein complex; protein crosslink; protein degradation; protein protein interaction; protein structure; rapid growth; success; supportive environment; transposon sequencing; vaccine delivery; yeast two hybrid system; Agriculture; Animal Diseases; Anthrax disease; Botulism; Cells; Cellular Structures; Colitis; Cytoplasmic Protein; Decontamination; Effectiveness; Elements; Environment; Enzymes; Event; Food; Food Poisoning; Gene Proteins; Genes; Genetic; Germination; Goals; Growth; Hour; Hydration status; Industrialization; Infection; Knowledge; Lead; Life; Lipids; Membrane; Membrane Fluidity; Membrane Proteins; Metabolic; Metabolism; Methods; Modification; Multiprotein Complexes; Organism; Pathogenesis; Peptide Hydrolases; Planet Earth; Play; Procedures; Process; Property; Protease Inhibitor; Proteins; Proteolysis; Reproduction spores; Resistance; Role; Structure; Surface; Tetanus; Work; base; gene discovery; human disease; improved; mutant; novel; physical assault; prevent; protein complex; protein crosslink; protein degradation; protein protein interaction; protein structure; rapid growth; success; supportive environment; transposon sequencing; vaccine delivery; yeast two hybrid system

Abstract Bacterial endospores are the most persistent and resistant forms of life on earth, able to remain in dormancy for decades and to survive a range of potential killing treatments that no other organisms can approach. Amazingly, these dormant cells can sense a growth-supportive environment and return to vegetative growth within hours through the process of germination. Major spore-specific modifications to cell structure and cellular content drive dormancy and resistance to killing treatments, and the dormant spores possess mechanisms to rapidly reverse these modifications during germination. The long-term goal of this study is to fully understand the details of cellular modifications that determine spore properties, the mechanism by which the spore initiates germination, and the cascade of events that lead to a resumption of metabolism and growth Cytoplasmic proteins are highly stabilized in the dehydrated spore core, but most germination-active proteins are on the membrane outer surface, in a hydrated environment, and must be stabilized during long-term dormancy and potential physical assault by other mechanisms. The overriding hypothesis of the proposed work is that the majority of the germination sensing and regulating apparatus is found in very stable multiprotein complexes in or on the inner spore membrane, which serves as a uniquely stable platform due to its minimal membrane fluidity. The specific goals of the proposed work are to define the components of these protein complexes, to examine potentially unique modifications of the membrane structure, and to examine the degradation of spore membrane proteins and effects this has on progression of germination. The proposed work also includes screens for discovery of genes that play previously unknown roles in the germination process. Spores play important roles in the initiation of several human and animal diseases, and in contamination and degradation of food products. Spores are used as the highly stable vehicles for the delivery of desirable metabolic activities in many industrial and agricultural products, and have been developed as stable vehicles for vaccine delivery. In all of these cases, spore germination plays a key role in the success of the process: pathogenesis or delivery of an activity. A full understanding of germination can therefore drive methods to avoid or improve these processes. Blocking germination can prevent pathogenesis, while stimulating highly efficient germination renders the spores susceptible to much simpler decontamination methods. Stimulating higher germination efficiency or rate can improve the effectiveness of a spore-based product.

抽象的 细菌内孢子是地球上最持久和抗性的生命形式，能够留在 几十年 方法。令人惊讶的是，这些休眠的细胞可以感觉到一个支持生长的环境并恢复营养 在发芽过程中数小时内增长。对细胞结构和细胞结构的主要孢子特异性修饰 细胞含量驱动休眠和抵抗杀死治疗，休眠孢子具有 在发芽过程中迅速扭转这些修饰的机制。这项研究的长期目标是 充分了解确定孢子性能的细胞修饰细节 孢子引发发芽，以及导致新陈代谢和生长恢复的事件级联 细胞质蛋白在脱水的孢子核中高度稳定，但大多数发芽活性 蛋白质在膜外表面，在水合环境中，必须在长期内稳定 其他机制受到休眠和潜在的身体攻击。拟议工作的推翻假设 是在非常稳定的多蛋白中发现大多数发芽传感和调节设备 内部或内部孢子膜中的复合物，由于其最小 膜流动性。拟议工作的具体目标是定义这些蛋白质的组成部分 复合物，检查膜结构的潜在独特修饰，并检查 孢子膜蛋白的降解及其对发芽进展的影响。拟议的工作 还包括用于发现基因在发芽过程中扮演未知角色的基因的屏幕。 孢子在几种人类和动物疾病的启动和污染中起着重要作用 和食品的降解。孢子被用作提供理想的高度稳定车辆 许多工业和农产品中的代谢活动，已被开发为稳定的车辆 疫苗输送。在所有这些情况下，孢子的发芽在该过程的成功中都起着关键作用： 活性的发病机理或传递。因此，完全了解发芽可以推动方法避免 或改进这些过程。阻止发芽可以防止发病机理，同时刺激高效 发芽使孢子易受更简单的净化方法。刺激更高 发芽效率或速率可以提高基于孢子的产品的有效性。