Function of the Bacillus anthracis Spore Carboydrate

炭疽芽孢杆菌孢子碳酸盐的功能

• 批准号: 7068847
• 负责人: GEORGE C. STEWART
• 金额: $ 5.07万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 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 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7068847
• 关键词: Bacillus anthracis; anthrax; bacterial genetics; bioterrorism /chemical warfare; carbohydrate biosynthesis; carbohydrates; electron microscopy; gel electrophoresis; gene deletion mutation; gene targeting; glycoproteins; guinea pigs; laboratory rabbit; mass spectrometry; microorganism immunology; protein structure function; spores; virulence; virus protein

DESCRIPTION (provided by applicant): Because of the highly fatal nature of pulmonary anthrax, the ease of production and storage of the spores of B. anthracis, and their survival in the environment after an attack, this bacterium has become the primary agent in biowarfare and bioterrorism. The window of opportunity for effective antibiotic treatment of patients with pulmonary anthrax is so small that vaccination is the current best defense against the disease. The spore of B. anthracis is the actual infectious agent and the form of the organism that is involved with the first interactions with the host macrophages. Recent studies have found that spore antigens are an important component to immunity against anthrax. We have identified a unique carbohydrate component of the spore. It is not known what roles carbohydrates play in the biology of the spore, from any species of bacteria. In this project, we will create mutants, which deleted for B. anthracis spore glycoprotein genes. The effect of these gene knockouts on spore carbohydrate content will be determined by mass spectrometry. The mutant cells will be evaluated for defects in spore formation and the spores from these mutants characterized for their resistance properties and germination efficiency in vitro. The role of the carbohydrate and protein components of the exosporium glycoprotein in conferring immunity to infection will be assessed. Preliminary experiments will be carried out to determine if loss of the BclA glycoprotein of B. anthracis affects the virulence properties of this anthrax agent. These studies will provide the information to evaluate whether the spore carbohydrate would be useful as an immunogen in a vaccine against anthrax. The results will provide supporting data for a future proposal to more specifically correlate spore surface structures with virulence and as vaccine targets.

描述（由申请人提供）：由于肺炭疽具有高度致命性，炭疽芽孢杆菌孢子易于生产和储存，并且它们在受到攻击后能够在环境中生存，因此这种细菌已成为生物战的主要病原体和生物恐怖主义。对肺炭疽患者进行有效抗生素治疗的机会窗口非常小，因此疫苗接种是目前预防该疾病的最佳方法。炭疽芽孢杆菌的孢子是实际的传染原，也是参与与宿主巨噬细胞首次相互作用的生物体形式。最近的研究发现，孢子抗原是炭疽免疫的重要组成部分。我们已经确定了孢子的独特碳水化合物成分。目前尚不清楚碳水化合物在任何细菌物种的孢子生物学中发挥什么作用。在这个项目中，我们将创建删除炭疽芽孢杆菌孢子糖蛋白基因的突变体。这些基因敲除对孢子碳水化合物含量的影响将通过质谱法测定。将评估突变细胞的孢子形成缺陷，并表征这些突变体的孢子的抗性特性和体外发芽效率。将评估孢子外糖蛋白的碳水化合物和蛋白质成分在赋予感染免疫力中的作用。将进行初步实验以确定炭疽芽孢杆菌 BclA 糖蛋白的缺失是否会影响该炭疽菌的毒力特性。这些研究将提供信息来评估孢子碳水化合物是否可用作炭疽疫苗中的免疫原。研究结果将为未来的提议提供支持数据，以更具体地将孢子表面结构与毒力和作为疫苗靶标相关联。