Barisch Caroline, Soldati Thierry
Department of Biochemistry, Faculty of Sciences, University of Geneva, 30 quai Ernest-Ansermet, Science II, 1211, Geneva-4, Switzerland.
Department of Biochemistry, Faculty of Sciences, University of Geneva, 30 quai Ernest-Ansermet, Science II, 1211, Geneva-4, Switzerland.
Biochimie. 2017 Oct;141:54-61. doi: 10.1016/j.biochi.2017.06.001. Epub 2017 Jun 3.
Tuberculosis (Tb) is a lung infection caused by Mycobacterium tuberculosis (Mtb). With one third of the world population latently infected, it represents the most prevalent bacterial infectious diseases worldwide. Typically, persistence is linked to so-called "dormant" slow-growing bacteria, which have a low metabolic rate and a reduced response to antibiotic treatments. However, dormant bacteria regain growth and virulence when the immune system is weakened, leading again to the active form of the disease. Fatty acids (FAs) released from host triacylglycerols (TAGs) and sterols are proposed to serve as sole carbon sources during infection. The metabolism of FAs requires beta-oxidation as well as gluconeogenesis and the glyoxylate shunt. Interestingly, the Mtb genome encodes more than hundred proteins involved in the five reactions of beta-oxidation, clearly demonstrating the importance of lipids as energy source. FAs have also been proposed to play a role during resuscitation, the resumption of replicative activities from dormancy. Lipid droplets (LDs) are energy and carbon reservoirs and have been described in all domains. TAGs and sterol esters (SEs) are stored in their hydrophobic core, surrounded by a phospholipid monolayer. Importantly, host LDs have been described as crucial for several intracellular bacterial pathogens and viruses and specifically translocate to the pathogen-containing vacuole (PVC) during mycobacteria infection. FAs released from host LDs are used by the pathogen as energy source and as building blocks for membrane synthesis. Despite their essential role, the mechanisms by which pathogenic mycobacteria induce the cellular redistribution of LDs and gain access to the stored lipids are still poorly understood. This review describes recent evidence about the dual interaction of mycobacteria with host LDs and membrane phospholipids and integrates them in a broader view of the underlying cellular processes manipulated by various intracellular pathogens to gain access to host lipids.
结核病（Tb）是由结核分枝杆菌（Mtb）引起的肺部感染。全球三分之一的人口处于潜伏感染状态，它是全球最普遍的细菌性传染病。通常，持续性感染与所谓的“休眠”缓慢生长细菌有关，这些细菌代谢率低，对抗生素治疗的反应减弱。然而，当免疫系统减弱时，休眠细菌会恢复生长和毒力，再次导致疾病的活跃形式。宿主三酰甘油（TAGs）和甾醇释放的脂肪酸（FAs）被认为在感染期间作为唯一的碳源。脂肪酸的代谢需要β-氧化以及糖异生和乙醛酸循环。有趣的是，Mtb基因组编码了一百多种参与β-氧化五个反应的蛋白质，清楚地证明了脂质作为能量来源的重要性。脂肪酸也被认为在复苏过程中发挥作用，即从休眠状态恢复复制活动。脂滴（LDs）是能量和碳的储存库，在所有领域都有描述。TAGs和甾醇酯（SEs）储存在其疏水核心中，周围是磷脂单分子层。重要的是，宿主脂滴已被描述为对几种细胞内细菌病原体和病毒至关重要，并且在分枝杆菌感染期间特异性地转运到含病原体的液泡（PVC）中。病原体利用宿主脂滴释放的脂肪酸作为能量来源和膜合成所需的构件。尽管它们起着至关重要的作用，但致病性分枝杆菌诱导脂滴细胞重新分布并获取储存脂质的机制仍知之甚少。本综述描述了关于分枝杆菌与宿主脂滴和膜磷脂双重相互作用的最新证据，并将它们整合到更广泛的细胞过程中，这些过程被各种细胞内病原体操纵以获取宿主脂质。
