Gene Expression in Mycobacterium Tuberculosis

结核分枝杆菌中的基因表达

• 批准号: 7060710
• 负责人: JOSEPHINE E CLARK-CURTISS
• 金额: $ 32.59万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7060710
• 关键词: Mycobacterium tuberculosis; antiserum; bacterial genetics; gene expression; growth media; human subject; laboratory rabbit; macrophage; microorganism culture; microorganism growth; phlebotomy; regulatory gene; virulence

DESCRIPTION (provided by applicant): Tuberculosis, one of the great scourges of humankind, continues to be a serious and significant health problem in the world today. The World Health Organization estimates that one-third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of TB. Approximately 8 million new cases of TB are diagnosed annually worldwide. Of those individuals with active disease, nearly 2 million die each year. Small wonder, then that in 1993, WHO declared tuberculosis to be a global health emergency, as it remains today. During the past 12-14 years, significant progress has been made in the development of genetic tools to facilitate analysis of the genes and gene products of M. tuberculosis. The nucleotide sequences of the entire genomes of two strains of M. tuberculosis have been determined. The techniques of DNA microarray analysis and two-dimensional gel electrophoresis analysis have provided valuable information about global gene expression and protein production by M. tuberculosis grown in defined environments. We developed a method to identify M. tuberculosis genes that are expressed when the mycobacteria are growing in their favored ecological niche, the human macrophage. Although much has been learned, fundamental aspects of M. tuberculosis pathogenesis remain unknown. Employing a number of currently available genetic, genomic, proteomic, and molecular biological tools, we propose to (1) characterize the regulons of the TrcRS, Rv1626, and PrrAB regulatory systems, (2) determine the contribution of specific gene products to M. tuberculosis pathogenesis by comparisons between wild-type M. tuberculosis H37Rv and strains of H37Rv with mutations in specific genes expressed during growth in human macrophages and (3) compare gene expression by M. tuberculosis growing in human peripheral blood monocyte-derived macrophages and in infected mouse lungs by cDNA microarray and quantitative RT-PCR (QRT-PCR) analyses.

描述（由申请人提供）：结核病是人类的巨大祸害之一，在当今世界上仍然是严重而重大的健康问题。世界卫生组织估计，世界人口中有三分​​之一感染了结核分枝杆菌，这是结核病的病因。每年在全球范围内诊断出大约800万例新的结核病病例。在那些患有活跃疾病的人中，每年将近200万人死亡。不好意思，然后在1993年宣布结核病为全球卫生紧急情况，如今仍然如此。 在过去的12 - 4年中，在开发遗传工具方面取得了重大进展，以促进分析结核分枝杆菌的基因和基因产物。已经确定了两种结核分枝杆菌菌株的整个基因组的核苷酸序列。 DNA微阵列分析和二维凝胶电泳分析的技术提供了有关在定义的环境中生长的结核病的全球基因表达和蛋白质产生的宝贵信息。我们开发了一种方法来鉴定分枝杆菌在其受青睐的生态生态位，人类巨噬细胞增长时表达的结核分枝杆菌基因。 尽管已经学到了很多东西，但结核分枝杆菌发病机理的基本方面仍然未知。 Employing a number of currently available genetic, genomic, proteomic, and molecular biological tools, we propose to (1) characterize the regulons of the TrcRS, Rv1626, and PrrAB regulatory systems, (2) determine the contribution of specific gene products to M. tuberculosis pathogenesis by comparisons between wild-type M. tuberculosis H37Rv and strains of H37Rv with mutations in在人类巨噬细胞生长过程中表达的特定基因，（3）通过在人外周血单核细胞衍生的巨噬细胞中生长的结核分枝杆菌和通过cDNA微阵列和感染小鼠肺的基因表达进行比较。