Function of the Bacillus anthracis Spore Carboydrate

描述（由申请方提供）：由于肺炭疽的高度致命性，B的孢子易于生产和储存。炭疽杆菌，以及它们在攻击后在环境中的存活，这种细菌已经成为生物战和生物恐怖主义的主要媒介。对肺炭疽病患者进行有效抗生素治疗的机会之窗非常小，因此接种疫苗是目前对抗该疾病的最佳防御措施。B的孢子。炭疽菌是真正的感染因子，是与宿主巨噬细胞发生第一次相互作用的生物体形式。近年来研究发现，炭疽芽孢抗原是炭疽免疫的重要组成部分。我们已经鉴定出孢子中一种独特的碳水化合物成分。目前还不知道碳水化合物在任何种类的细菌孢子生物学中起什么作用。在这个项目中，我们将创建突变体，其中删除为B。炭疽孢子糖蛋白基因。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。将评价突变体细胞的孢子形成缺陷，并表征这些突变体的孢子的体外抗性和萌发效率。将评估外孢壁糖蛋白的碳水化合物和蛋白质组分在赋予对感染的免疫力中的作用。将进行初步实验以确定B的BclA糖蛋白的丢失是否会导致细胞凋亡。炭疽病影响这种炭疽病剂的毒力特性。这些研究将提供信息，以评估是否孢子碳水化合物将是有用的免疫原，在疫苗对炭疽。这些结果将为未来提出更具体地将孢子表面结构与毒力相关联并作为疫苗靶点的建议提供支持数据。

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.