Abuhammad Areej
School of Pharmacy, The University of Jordan, Amman, Jordan.
Br J Pharmacol. 2017 Jul;174(14):2194-2208. doi: 10.1111/bph.13694. Epub 2017 Jan 24.
Tuberculosis (TB), although a curable disease, is still one of the most difficult infections to treat. Mycobacterium tuberculosis infects 10 million people worldwide and kills 1.5 million people each year. Reactivation of a latent infection is the major cause of TB. Cholesterol is a critical carbon source during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into lipid virulence factors. The M. tuberculosis genome contains a large regulon of cholesterol catabolic genes suggesting that the microorganism can utilize host sterol for infection and persistence. The protein products of these genes present ideal targets for rational drug discovery programmes. This review summarizes the development of enzyme inhibitors targeting the cholesterol pathway in M. tuberculosis. This knowledge is essential for the discovery of novel agents to treat M. tuberculosis infection.
This article is part of a themed section on Drug Metabolism and Antibiotic Resistance in Micro-organisms. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.14/issuetoc.
结核病（TB）虽是可治愈的疾病，但仍是最难治疗的感染之一。结核分枝杆菌每年在全球感染1000万人，并导致150万人死亡。潜伏感染的重新激活是结核病的主要病因。胆固醇是潜伏感染期间的关键碳源。胆固醇的分解代谢有助于丙酰辅酶A库的形成，丙酰辅酶A是一种被整合到脂质毒力因子中的前体。结核分枝杆菌基因组包含一个由胆固醇分解代谢基因组成的大调节子，这表明该微生物可利用宿主甾醇进行感染和存活。这些基因的蛋白质产物是合理药物研发计划的理想靶点。本综述总结了针对结核分枝杆菌胆固醇途径的酶抑制剂的研究进展。这些知识对于发现治疗结核分枝杆菌感染的新型药物至关重要。
本文是关于微生物药物代谢与抗生素耐药性主题系列的一部分。若要查看本系列的其他文章，请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.14/issuetoc。
