Mycolic acid biosynthesis and processing in Mycobacterium tuberculosis

引起结核病的人类病原体结核分枝杆菌（MTB）含有一种富含脂质的“蜡状”细胞壁，可形成抵御恶劣环境的保护性屏障。分枝杆菌脂质不仅提供一个保护层，而且还参与与受感染宿主细胞的相互作用。此外，一些脂质成分对结核分枝杆菌的存活至关重要，因此催化其生物合成的酶是抗结核药物的潜在靶点。该项目旨在通过在候选基因中产生定义的MTB突变体，进一步了解这些脂质构建块是如何产生的。然后将对突变菌株进行脂质成分损失和/或中间化合物积累的测试。该研究还旨在通过在实验室感染模型中测试这些突变菌株来评估特定脂质在毒力中的作用。希望这些研究不仅能帮助我们寻找有效对抗结核病的新药，还能帮助我们找到更好的疫苗。

The tuberculosis-causing, human pathogen Mycobacterium tuberculosis (MTB) contains a lipid rich ‘waxy‘ cell wall that forms a protective barrier against harsh environments. Mycobacterial lipids not only offer a protective cover, but are also involved in interactions with infected host cells. Furthermore, some lipid components are essential for the survival of MTB and thus the enzymes that catalyze their biosynthesis represent potential targets for antimycobacterial drugs. The proposed project aims to further our understanding about how these lipid building blocks are made by generating defined mutants of MTB in candidate genes. The mutant strains will then be tested for loss of lipid components and/or accumulation of intermediate compounds. The study also aims to assess the role of specific lipids in virulence by testing these mutant strains in laboratory models of infection. The hope is that these studies will aid in our search not only for new drugs effective against tuberculosis, but also a better vaccine.