TWO-COMPONENT SYSTEMS OF MYCOBACTERIUM TUBERCULOSIS

描述（改编自申请人的提案）：本提案是 根据申办者实验室正在进行的研究， 结核分枝杆菌发病机制。本研究探讨 双组分信号转导系统在 这种生物的毒性。 具体而言，申请人将描述MtrA的作用- MtrB双组分系统在M.结核 在主机内。因为这个系统中的响应调节器是 在巨噬细胞感染后激活，假设这是 可能需要双组分系统（可能还有其他）， 在宿主体内生存。该假设将通过以下方式进行检验：（1） 干扰M.结核病和检测 其对培养的巨噬细胞和小鼠体内毒力的影响 （2）鉴定和表征MtrA调控的基因; 以及（3）确定来自其它双组分的响应调节剂是否 系统也在宿主的吞噬细胞内受到调节。

DESCRIPTION (Adapted from the applicant's proposal): This proposal is based on the ongoing research in the sponsorÕs laboratory on Mycobacterium tuberculosis pathogenesis. This study investigates the role that two-component signal transduction systems play in the virulence of this organism. Specifically, the applicant will characterize the role that the MtrA- MtrB two-component system plays in the survival of M. tuberculosis within the host. Because the response regulator in this system is activated upon infection of macrophages, the hypothesis is that this two-component system (and presumably others as well) may be required for survival within the host. This hypothesis will be tested by: (1) disrupting the mtrA response regulator in M. tuberculosis and testing its effect on virulence within cultured macrophages and within a murine host; (2) identifying and characterizing the genes regulated by MtrA; and (3) determining whether response regulators from other two-component systems are also regulated within phagocytic cells of the host.