STRATEGIES FOR INACTIVATING BACILLUS ANTHRACIS SPORES

灭活炭疽杆菌孢子的策略

• 批准号: 6534304
• 负责人: Arthur I. Aronson
• 金额: $ 19.15万
• 依托单位: PURDUE UNIVERSITY CALUMET CAMPUS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-29 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6534304
• 关键词: Bacillus anthracis; anthrax; antibacterial agents; bacterial proteins; communicable disease control; microorganism culture; protein structure function; spores

Bacillus anthracis is an animal and human pathogen with potential as a biological warfare agent. It is a spore-forming Bacillus with pathogenicity due to plasmid genes encoding three toxin components and a polyglutamic acid capsule. Its effectiveness as an agent is due to the ease of producing and spreading the spores. These spores are dormant and very resistant to a variety of stress conditions such as heat, ultraviolet radiation, and chemical treatment. The spores can thus remain in the soil or phylloplane for many years. Under suitable conditions, they can germinate and vegetative cells will propagate in the soil and then resporulate. Thus, there is an enormous potential for sustaining and spreading this organism once it has been dispersed. The spore is surrounded by a multilayered proteinaceous coat that accounts for much of its resistance properties and contributes to the capacity of the spore to respond to germinants and propagate as vegetative cells. A detailed understanding of the spore coat structure, how it is assembled, and how it can be specifically disrupted would provide an effective way for controlling this bioweapon. Information gleaned from extensive studies of Bacillus subtilis spore coat assembly and the function of the 25 or so proteins that make up the coat layers of this species will be used to isolate and characterize spore coat protein genes from B. anthracis. This will be done in part by identifying B. subtilis homologues in the B. anthracis genome and in part by reverse genetics using the amino acid sequences of purified B. anthracis coat proteins. These genes will be disrupted and the effects of such null mutations on spore coat assembly and structure determined. Some features of the B. anthracis spore such as germination response and spore coat structure have been shown to vary with the conditions used for spore formation. Most significantly, culture conditions that induce many pathogenicity genes, including the toxin genes, resulted in a major change in the spore coat protein profile. This correlation may reflect coordination between pathogenicity due to toxin synthesis and encapsulation of vegetative cells and special spore properties that could enhance infectivity. The nature of the spore coat changes and their contribution to spore germination and resistance will be examined. This information about spore coat composition and its variation with culture conditions will be exploited to find specific reagents and procedures for destroying the spore or for inhibiting germination. Once such reagents or methods have been identified, they will be tested on spores in various soils that should mimic natural environments and thus the conditions needed for the effective control of this bioweapon.

炭疽杆菌是一种动物和人类的病原体， 作为一种生物战 剂 这是一种孢子形成 芽孢 由于编码三种毒素组分的质粒基因和 聚谷氨酸胶囊它作为代理人的有效性是由于易于 产生和传播孢子。 这些孢子处于休眠状态， 耐各种应力条件，如热，紫外线 辐射和化学处理。因此，孢子可以留在土壤中， 多年来的Phylloplane。在适当的条件下，它们可以发芽， 营养细胞将在土壤中繁殖，然后再产生孢子。 因此 是维持和传播这种生物的巨大潜力， 已经被驱散了孢子被一层多层蛋白质包裹 涂层占其电阻性能的大部分，并有助于 孢子对萌发物作出反应并作为营养体繁殖的能力 细胞 详细了解孢子的外被结构， 组装，以及如何能够具体破坏将提供一个有效的 控制生化武器的方法从广泛的研究中收集的信息 枯草芽孢杆菌的孢子衣组装和功能的25个左右 构成这种物种的外壳层的蛋白质将被用来分离 并表征来自B的孢子外壳蛋白基因。炭疽病为此将 部分通过识别B。 在B.炭疽菌基因组和 部分通过使用纯化的B的氨基酸序列的反向遗传学。 炭疽菌外壳蛋白这些基因将被破坏， 孢子外壳组装上的无效突变和确定的结构。一些特征 是B的。 炭疽孢子如萌发反应和孢子衣 结构已被证明是不同的条件下使用的孢子 阵 最重要的是， 文化 条件 诱导 许多 致病基因，包括毒素基因，导致了一个重大的变化， 孢子外壳蛋白图谱。这种相关性可能反映了协调 毒素合成引起的致病性和营养体的包囊性之间的关系 细胞和特殊的孢子特性，可以提高感染力。性质 孢子外壁的变化及其对孢子萌发的贡献， 阻力将受到考验。这些关于孢子衣成分的信息， 其随培养条件的变化将被利用以找到特定的 试剂和方法 为了消灭 孢子或形成 抑制 萌发一旦确定了这些试剂或方法， 在模拟自然环境的各种土壤中对孢子进行了测试， 从而达到有效控制这种生物武器所需要的条件。