Defining the role of host lipid repertoire in Mycobacterium tuberculosis infection

项目摘要/摘要 世界上近三分之一的人口感染了结核分枝杆菌。这个水库贡献了 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。多重耐药菌株的出现与低诊断和治疗覆盖率相结合 许多发展中国家的结核病加重了结核病造成的疾病负担。取得的巨大成功 结核分枝杆菌致病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。我们对此的理解 这些过程，特别是在结核分枝杆菌感染背景下的宿主脂质生物学 是有限的。这项拟议工作的目的是研究宿主的脂质生物合成在进入、复制 和杀死结核分枝杆菌。为此，单个敲除的巨噬细胞系缺乏 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.