PDF(Pubmed)
Abstract：
Mycobacterium tuberculosis causes tuberculosis (TB), one of the world\'s most deadly infections. Lipids play an important role in M. tuberculosis pathogenesis. M. tuberculosis grows intracellularly within lipid-laden macrophages and extracellularly within the cholesterol-rich caseum of necrotic granulomas and pulmonary cavities. Evolved from soil saprophytes that are able to metabolize cholesterol from organic matter in the environment, M. tuberculosis inherited an extensive and highly conserved machinery to metabolize cholesterol. M. tuberculosis uses this machinery to degrade host cholesterol; the products of cholesterol degradation are incorporated into central carbon metabolism and used to generate cell envelope lipids, which play important roles in virulence. The host also modifies cholesterol by enzymatically oxidizing it to a variety of derivatives, collectively called oxysterols, which modulate cholesterol homeostasis and the immune response. Recently, we found that M. tuberculosis converts host cholesterol to an oxidized metabolite, cholestenone, that accumulates in the lungs of individuals with TB. M. tuberculosis encodes cholesterol-modifying enzymes, including a hydroxysteroid dehydrogenase, a putative cholesterol oxidase, and numerous cytochrome P450 monooxygenases. Here, we review what is known about cholesterol and its oxidation products in the pathogenesis of TB. We consider the possibility that the biological function of cholesterol metabolism by M. tuberculosis extends beyond a nutritional role.
摘要：
结核分枝杆菌导致结核病（TB），世界上最致命的感染之一。脂质在结核分枝杆菌发病机制中起重要作用。结核分枝杆菌在充满脂质的巨噬细胞内在胞内生长，并在坏死肉芽肿和肺腔的富含胆固醇的病例内在胞外生长。从土壤腐生植物进化而来，这些腐生植物能够从环境中的有机物质中代谢胆固醇，结核分枝杆菌遗传了一种广泛且高度保守的代谢胆固醇的机制。结核分枝杆菌使用这种机制来降解宿主胆固醇；胆固醇降解的产物被整合到中心碳代谢中，并用于产生细胞包膜脂质，在毒力中起重要作用。宿主还通过将其酶促氧化为各种衍生物来修饰胆固醇，统称为氧固醇，调节胆固醇稳态和免疫反应。最近,我们发现结核分枝杆菌将宿主胆固醇转化为氧化的代谢产物，choestenone,积聚在结核病患者的肺部。结核分枝杆菌编码胆固醇修饰酶，包括羟基类固醇脱氢酶，一种推定的胆固醇氧化酶,和许多细胞色素P450单加氧酶。这里,我们综述了胆固醇及其氧化产物在结核病发病机制中的作用。我们考虑结核分枝杆菌胆固醇代谢的生物学功能超出营养作用的可能性。
