GENE EXPRESSION IN MYCOBACTERIUM TUBERCULOSIS

结核分枝杆菌中的基因表达

基本信息

批准号：
6628013
负责人：
JOSEPHINE E CLARK-CURTISS
金额：
$ 26.78万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-02-01 至 2004-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6628013
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

项目摘要

Tuberculosis, one of the great scourges of humankind, is the leading cause of death worldwide from a single infectious disease. Although the incidence of TB has again begun to decline in the U.S., TB remains a significant health problem in this country, most frequently affecting the elderly, the homeless, individuals with AIDS and immigrants from nations where TB is endemic. Although the causative agent of TB, Mycobacterium tuberculosis, was identified a century ago, knowledge about fundamental physiological capabilities, the genetics and the mechanisms of pathogenicity of M. tuberculosis is only now beginning to emerge. We have identified several genes which are expressed by M. tuberculosis H37Rv when the bacilli are growing in human macrophages in culture, but which are not expressed by the bacilli when they are growing in laboratory broth culture. We hypothesize that these genes and their products may be important in the survival and growth of M. tuberculosis in macrophages and may contribute to the pathogenicity of the tubercle bacilli. We propose to (1) determine the contribution of specific macrophage-expressed gene products to survival and growth of M. tuberculosis in macrophages by molecular and genetic characterization of genes on a cosmid that appear to be coordinately expressed, a putative response regulator gene, and mceD, a gene that has been shown to enhance survival of E. coli in cultured macrophages; and (2) to identify and characterize genes and gene products of M. tuberculosis that are expressed at early times after phagocytosis, at late times, and throughout growth in human macrophages in culture.

结核病是人类的巨大祸害之一，是全世界死亡的主要原因。尽管美国结核病的发病率在美国再次开始下降，但结核病仍然是该国的重大健康问题，最常见地影响老年人，无家可归者，有艾滋病和移民的人来自特有结核病的国家。尽管TB的致病药物是结核分枝杆菌的病因，但在一个世纪前确定了有关基本生理能力，结核分枝杆菌病致病性的基本能力的知识，直到现在才开始出现。我们已经确定了几种基因，这些基因在培养基中人类巨噬细胞中生长时结核分枝杆菌H37RV表达，但在实验室肉汤培养中生长时，它们并未由杆菌表达。我们假设这些基因及其产物在巨噬细胞中结核分枝杆菌的生存和生长中可能很重要，并且可能有助于结核菌的致病性。 We propose to (1) determine the contribution of specific macrophage-expressed gene products to survival and growth of M. tuberculosis in macrophages by molecular and genetic characterization of genes on a cosmid that appear to be coordinately expressed, a putative response regulator gene, and mceD, a gene that has been shown to enhance survival of E. coli in cultured macrophages; （2）识别和表征结核分枝杆菌的基因和基因产物，这些基因和基因产物在吞噬作用后早期表达，在培养物中以及人类巨噬细胞的整个生长中。