STRATEGIES FOR INACTIVATING BACILLUS ANTHRACIS SPORES

灭活炭疽杆菌孢子的策略

• 批准号: 6216821
• 负责人: Arthur I. Aronson
• 金额: $ 22.86万
• 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 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6216821
• 关键词: Bacillus; 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.

炭疽杆菌是一种具有潜在潜力的动物和人类病原体 作为生物战剂。 它是一种芽孢杆菌，具有 致病性归因于编码三种毒素成分和一种的质粒基因 聚谷氨酸胶囊。其作为代理的有效性是由于其易于 产生并传播孢子。 这些孢子处于休眠状态并且非常 能抵抗多种压力条件，如热、紫外线 辐射和化学处理。因此，孢子可以保留在土壤中或 叶面多年。在适宜的条件下，它们可以发芽 营养细胞将在土壤中繁殖，然后再形成孢子。 因此，有 一旦这种生物体存在，它就具有维持和传播的巨大潜力 已被驱散。孢子被多层蛋白质包围 涂层占其大部分抵抗性能并有助于 孢子对萌芽作出反应并以营养方式繁殖的能力 细胞。 详细了解孢子衣结构，它是怎样的 组装起来，以及如何具体破坏它，将提供一种有效的方法 控制这种生物武器的方法。 Information gleaned from extensive studies 枯草芽孢杆菌孢子衣的组装及功能 25 左右 构成该物种外壳层的蛋白质将用于分离 并表征炭疽芽孢杆菌的孢子外壳蛋白基因。这将完成 部分是通过识别炭疽芽孢杆菌基因组中的枯草芽孢杆菌同源物， 部分通过使用纯化 B. 的氨基酸序列进行反向遗传学。 炭疽外壳蛋白。这些基因将被破坏，这种影响 确定孢子衣组装和结构的无效突变。一些功能 炭疽芽孢杆菌孢子的特征，例如萌发反应和孢子衣 结构已被证明随孢子使用的条件而变化 形成。 最重要的是，培养条件可诱导许多 致病基因，包括毒素基因，导致了 孢子外壳蛋白谱。这种相关性可能反映了协调性 毒素合成和营养体包封引起的致病性之间 细胞和特殊的孢子特性可以增强传染性。大自然 孢子外壳的变化及其对孢子萌发的贡献 将检查电阻。有关孢子衣成分的信息和 将利用其随培养条件的变化来寻找特定的 用于破坏孢子或抑制孢子的试剂和程序 发芽。一旦确定了此类试剂或方法，它们将被 在模拟自然环境的各种土壤中的孢子上进行了测试 因此，需要有效控制这种生物武器的条件。