CHARACTERIZATION OF TWO NOVEL PATHWAYS IN MYCOBACTERIUM AS TARGETS AGAINST TUBER

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 结核分枝杆菌是一种导致结核病的细菌病原体，世界？最致命的传染病，每年夺去大约200万人的生命。目前，全世界每三人中就有一人感染结核分枝杆菌，结核病也是目前艾滋病患者的主要死因。最近的数据表明，以前未知的血红素获取系统在结核分枝杆菌的发病机制中起着重要作用。我建议的研究集中在获得对这一新的分枝杆菌血红素获取系统的结构理解。此外，我的建议包括一种新的途径，该途径被认为与脂肪酸代谢有关，已被证明是鼠疫耶尔森菌在巨噬细胞中生存所必需的，而结核分枝杆菌也有一条相应的途径。这些蛋白质的结构特征将使我们能够对这一重要途径进行功能表征。在SSRL束线上的时间对于了解这些途径中涉及的蛋白质的结构至关重要，目标是基于结构的药物设计，用于开发抗结核病(TB)的治疗药物，包括多药耐药菌株和潜在的结核病感染。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mycobacterium tuberculosis is a bacterial pathogen that causes tuberculosis, the worlds? most deadly infectious disease, which kills approximately two million people per year. Currently, one in three persons worldwide is infected with M. tuberculosis, and TB is also the current leading cause of death for AIDS patients. Recent data suggests that a previously uncharacterized heme acquisition system plays an important role in M. tuberculosis pathogenesis. My proposed research focuses on gaining a structural understanding of this novel mycobacterial heme acquisition system. Also, my proposal includes a novel pathway supposedly involved in fatty acid metabolism that has been shown to be essential for survival of Yersinia pestis in macrophages, and M. tuberculosis has a homologous pathway. Structural characterization of these proteins will allow us to functional characterize this important pathway. Time at the SSRL beam-line is paramount to the structural understanding of the proteins involved in these pathways with a goal of structure-based drug design for the development of therapeutics against tuberculosis (TB), which includes multi-drug resistant strains and latent TB infection.