TWO-COMPONENT SYSTEMS OF MYCOBACTERIUM TUBERCULOSIS

描述(改编自申请人的建议书)：本建议书 基于发起人S实验室正在进行的研究 结核分枝杆菌的发病机制。这项研究调查了 双组分信号转导系统在细胞周期调控中的作用 这种有机体的毒性。 具体地说，申请人将描述MTRA的角色- MTRB双组分系统在结核分枝杆菌存活中的作用 在主机内。因为这个系统中的响应调节器是 在巨噬细胞感染后被激活，假设这是 可能需要双组件系统(可能也需要其他组件) 在宿主体内生存。这一假设将通过以下方式进行检验：(1) 在结核分枝杆菌和检测中扰乱MTRA反应调节器 它对培养巨噬细胞和小鼠体内毒力的影响 (2)鉴定和鉴定MTRA调控的基因； 以及(3)确定来自其他双组分的响应调节器 这些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.