VIRULENCE GENE EXPRESSION BY BACILLUS ANTHRACIS

炭疽杆菌的毒力基因表达

• 批准号: 6076141
• 负责人: THERESA M. KOEHLER
• 金额: $ 20万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-12-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6076141
• 关键词: Bacillus; bacterial capsules; bacterial genetics; bacterial toxins; carbon dioxide; gene expression; gene mutation; genetic regulation; genetic regulatory element; host organism interaction; molecular cloning; protein biosynthesis; regulatory gene; site directed mutagenesis; transposon /insertion element; virulence

DESCRIPTION (Adapted from the applicant's abstract): To be successful pathogens, bacteria must possess mechanisms for sensing specific host environments, processing changes, and making appropriate adaptations. In many bacteria, expression of disparate virulence factors is controlled by a common regulatory system. Virulence gene expression in Bacillus anthracis, the causative agent of anthrax, is a unique example of a coordinately regulated response to a specific host-related signal. Virulent Bacillus anthracis produce two known virulence factors, a tripartite toxin, composed of edema factor, lethal factor, and protective antigen, and a poly-D-glutamic acid capsule. The toxin and capsule genes are located on plasmids pXO1 (185 kb) and pXO2 (95 kb), respectively. Synthesis of these virulence factors is enhanced when B. anthracis is grown in elevated levels of carbon dioxide. CO2 is postulated to be a physiologically significant signal during anthrax infection. Concentrations of bicarbonate and CO2 in mammalian tissues are comparable to those that activate toxin and capsule synthesis during in vitro growth. The long term goal of these studies is to elucidate the molecular basis for virulence gene expression in B. anthracis. The PI has determined that the trans-acting regulatory gene atxA is required for CO2-induced transcription of all three toxin genes during growth in vitro. AtxA also activates toxin expression in vivo; atxA mutants are avirulent in mice and mice infected with atxA- strains show a decreased immunological response to the toxin proteins. Another gene, acpA, has been implicated in CO2-induced capsule gene expression. In this study, the PI will further probe regulation of toxin and capsule synthesis and investigate whether B. anthracis harbors additional virulence genes. The specific aims are to: 1) identify atxA-regulated non-toxin genes and test the effect of these genes on virulence; 2) identify and characterize additional regulatory genes that affect toxin expression, 3) investigate the physiological significance of acpA expression in cells harboring atxA. These studies will provide information relevant to the pathogenesis of anthrax disease and increase knowledge concerning host-parasite relationships and signal transduction.

描述（根据申请人的摘要改编）：要成功 病原体，细菌必须具有传感特定宿主的机制 环境，处理更改并进行适当的适应。 在 许多细菌，不同的毒力因子的表达受A的控制 普通监管系统。 炭疽芽孢杆菌中的毒力基因表达， 炭疽病的病原体是协调的独特例子 对特定宿主相关信号的调节响应。 强大的芽孢杆菌 炭疽病产生两个已知的毒力因子，一种三方毒素，构成 水肿因子，致命因子和保护性抗原和A 聚-D-谷氨酸胶囊。 毒素和胶囊基因位于 质粒PXO1（185 kb）和PXO2（95 kb）。 这些的综合 当炭疽芽孢杆菌在升高的水平上生长时，毒力因子会增强 二氧化碳。 二氧化碳被认为是生理意义的 在炭疽感染期间信号。 碳酸氢盐和二氧化碳的浓度 哺乳动物组织与激活毒素和胶囊的组织相当 体外生长过程中的合成。 这些研究的长期目标是阐明分子基础 炭疽芽孢杆菌中的毒力基因表达。 PI已确定 二氧化碳诱导的转录需要跨作用调节基因ATXA 在体外生长过程中所有三种毒素基因中。 ATXA还激活毒素 体内表达； ATXA突变体在小鼠中是无毒的，感染的小鼠 与atxa-allains一起显示对毒素的免疫学反应降低 蛋白质。 另一个基因ACPA已与CO2诱导的胶囊有关 基因表达。 在这项研究中，PI将进一步探测 毒素和胶囊合成，并研究炭疽芽孢杆菌是否港口 其他毒力基因。 具体目的是：1）确定 ATXA调节的非毒素基因并测试这些基因对 毒力2）确定并表征其他调节基因 影响毒素表达，3）研究 携带ATXA的细胞中的ACPA表达。 这些研究将提供 与炭疽病的发病机理有关的信息并增加 有关宿主 - 寄生虫关系和信号转导的知识。