SPORE PEPTIDOGLYCAN DEGRADATION IN BACILLUS ANTHRACIS

炭疽杆菌中孢子肽聚糖的降解

• 批准号: 6873758
• 负责人: DAVID L POPHAM
• 金额: $ 24.65万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6873758
• 关键词: anthrax; antibacterial agents; bacteria infection mechanism; bacteriolysis; bioterrorism /chemical warfare; endopeptidases; enzyme activity; enzyme induction /repression; enzyme structure; gene mutation; genetic strain; high performance liquid chromatography; ion exchange chromatography; isomerase; mass spectrometry; peptide structure; peptidoglycan; protein purification; sporogenesis

DESCRIPTION (provided by applicant): The infectious agent in anthrax is the dormant B. anthracis spore, and establishment of infection requires germination and outgrowth of the spore. Degradation of the spore cortex peptidoglycan wall during germination is necessary to allow rehydration and resumption of metabolism in the spore core. Cortex lytic enzymes are present in an inactive form in the spore and are activated only in the presence of specific germinant molecules. Goals of the proposed studies are identification of the important B. anthracis cortex lytic enzymes, characterization of their activities, and understanding of the mechanisms for their activation. Structures of the peptidoglycan found in B. anthracis dormant and germinating spores will be determined in order to identify cortex lytic activities operating during germination. Genes predicted to encode cortex lytic enzymes, based upon sequence similarities, will be disrupted and changes in germination lytic activities in the mutant strains will be characterized. Cortex lytic enzymes will be extracted and purified from germinating B. anthracis spores. The enzymatic activities and identities of these proteins will be determined. A greater understanding of the process of spore cortex lysis will suggest possible methods for combating anthrax infection on two fronts. Identification of drugs or treatments that block cortex lysis will allow treatment of individuals exposed to spores to prevent establishment of infection. Identification of chemicals or treatments that activate cortex lysis, resulting in germination and rendering the spores susceptible to standard bactericidal agents, will allow easier decontamination of spore-contaminated sites and prevention of human exposure.

描述（由申请人提供）：炭疽病中的传染剂是休眠的B.炭疽孢子，建立感染需要孢子的发芽和生长。在发芽过程中，孢子皮层肽聚糖壁的降解是必要的，以使孢子核中的代谢补液和恢复。皮质裂解酶以孢子的非活性形式存在，仅在特定发芽分子的存在下被激活。拟议的研究的目标是鉴定重要的炭疽芽孢杆菌皮质裂解酶，其活性的表征以及对其激活机制的理解。为了鉴定发芽过程中运行的皮质裂解活性，将确定在炭疽芽孢杆菌休眠和发芽孢子中发现的肽聚糖的结构。预计将基于序列相似性编码皮层裂解酶的基因将被破坏，并且将表征突变菌株中的发芽裂解活性的变化。皮质裂解酶将从发芽的炭疽芽孢杆菌孢子中提取并纯化。这些蛋白质的酶活性和身份将被确定。对孢子皮质裂解的过程有更深入的了解，将提出可能在两个方面打击炭疽感染的可能方法。鉴定阻塞皮质裂解的药物或治疗方法将允许治疗暴露于孢子的个体，以防止建立感染。鉴定激活皮层裂解的化学物质或处理，导致发芽并使孢子易受标准杀菌剂的孢子，将使对孢子污染的部位更容易地进行净化并预防人类暴露。