Defining the role of host lipid repertoire in Mycobacterium tuberculosis infection

项目总结/摘要 近三分之一的世界人口感染结核分枝杆菌。这个水库 结核病发病率不断上升，每年约有1100万新病例和180万人死亡。 年多药耐药菌株的出现，加上低诊断和治疗覆盖率， 在许多发展中国家，结核病加重了疾病负担。的巨大成功 结核分枝杆菌在致病过程中依赖于其成功利用宿主细胞的能力， 包括脂质生物合成途径在内的破坏免疫系统的机制。我们理解 这些过程特别是结核分枝杆菌感染背景下宿主脂质生物学的过程 是有限的。本工作的目的是研究宿主的脂质生物合成在进入、复制中的作用 和杀死结核分枝杆菌。为此目的，单个敲除巨噬细胞细胞系缺乏 参与脂质生物合成的基因将使用CRISPR/Cas9技术产生。理解 这些途径或过程对结核分枝杆菌的生命周期至关重要，因为它们 代表了新疗法的潜在靶点。

PROJECT SUMMARY/ABSTRACT Nearly one-third of the world population is infected with Mycobacterium tuberculosis. This reservoir contributes towards an increasing incidence of tuberculosis, with about 11 million new cases and 1.8 million deaths every year. The emergence of multi-drug resistant strains combined with low diagnostic and therapeutic coverage in many developing countries, has worsened the disease burden caused by TB. The profound success of Mycobacterium tuberculosis in causing disease depends on its ability to successfully utilize the host’s cellular machineries including the lipid biosynthesis pathway to subvert the immune system. Our understanding of these processes especially that of the host lipid biology in the context of Mycobacterium tuberculosis infection is limited. The aim of the proposed work is to study the role of host’s lipid biosynthesis in the entry, replication and killing of Mycobacterium tuberculosis. For this purpose, individual knockout macrophage cell lines that lack genes involved in the biosynthesis of lipids will be generated using CRISPR/Cas9-technology. Understanding these pathways or processes essential for the life cycle of Mycobacterium tuberculosis is crucial, as they represent potential targets for new therapeutics.