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

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 细菌内生孢子是地球上最持久和最具抵抗力的生命形式，能够保留在 休眠数十年，并能在一系列其他生物体无法做到的潜在杀灭治疗中存活下来 方法。令人惊讶的是，这些休眠细胞可以感知支持生长的环境并恢复营养状态 通过发芽过程在数小时内生长。对细胞结构的主要孢子特异性修饰 细胞内容物驱动休眠和对杀灭处理的抵抗力，并且休眠孢子具有 在发芽过程中快速逆转这些修饰的机制。这项研究的长期目标是 充分了解决定孢子特性的细胞修饰的细节、其机制 孢子开始萌发，一系列事件导致新陈代谢和生长的恢复 细胞质蛋白在脱水孢子核心中高度稳定，但大多数具有萌发活性 蛋白质位于膜外表面，处于水合环境中，必须长期保持稳定 休眠和其他机制的潜在物理攻击。拟议工作的首要假设 大部分发芽传感和调节装置存在于非常稳定的多蛋白中 内孢子膜内或上的复合物，由于其最小的作用而成为独特稳定的平台 膜的流动性。拟议工作的具体目标是定义这些蛋白质的成分 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萌发进程的影响。拟议的工作 还包括筛选发现在发芽过程中发挥以前未知作用的基因。 孢子在多种人类和动物疾病的引发以及污染中发挥着重要作用 和食品的降解。孢子被用作高度稳定的载体来传递所需的物质 许多工业和农业产品的代谢活动，并已被开发为稳定的载体 疫苗递送。在所有这些情况下，孢子萌发对该过程的成功起着关键作用： 发病机制或活动的传递。因此，对发芽的充分了解可以推动避免 或改进这些流程。阻断发芽可预防发病，同时刺激高效 萌发使孢子易于采用更简单的净化方法。刺激更高 发芽效率或发芽率可以提高基于孢子的产品的有效性。