Mycobacterium tuberculosis induces decelerated bioenergetic metabolism in human macrophages.
Mycobacterium tuberculosis induces decelerated bioenergetic metabolism in human macrophages.
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DOI：
10.7554/elife.39169
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发表时间：
2018-11-16
期刊：
影响因子：
7.7
通讯作者：
Steyn AJ
中科院分区：
文献类型：
--
作者：
Cumming BM;Addicott KW;Adamson JH;Steyn AJ
结核分枝杆菌（Mtb）如何重新连接巨噬细胞的能量代谢以促进生存尚不清楚。在这里，我们使用细胞外通量分析同时实时测量糖酵解和呼吸速率。结核分枝杆菌感染诱导人单核细胞源性巨噬细胞出现静止能量表型，并通过糖酵解和TCA循环减慢通量。相比之下，感染疫苗株、牛分枝杆菌卡介苗或死亡结核分枝杆菌诱导糖酵解表型的通量更大。此外，Mtb降低了线粒体对葡萄糖的依赖性，增加了线粒体对脂肪酸的依赖性，将这种依赖性从未感染细胞中的内源性脂肪酸转移到感染巨噬细胞中的外源性脂肪酸。我们展示了宿主的可量化生物能量参数如何用于准确测量和跟踪疾病，这将使药物和疫苗功效的快速量化评估成为可能。我们的发现揭示了理解结核分枝杆菌宿主代谢重编程的生物能量基础的新范式。
How Mycobacterium tuberculosis (Mtb) rewires macrophage energy metabolism to facilitate survival is poorly characterized. Here, we used extracellular flux analysis to simultaneously measure the rates of glycolysis and respiration in real time. Mtb infection induced a quiescent energy phenotype in human monocyte-derived macrophages and decelerated flux through glycolysis and the TCA cycle. In contrast, infection with the vaccine strain, M. bovis BCG, or dead Mtb induced glycolytic phenotypes with greater flux. Furthermore, Mtb reduced the mitochondrial dependency on glucose and increased the mitochondrial dependency on fatty acids, shifting this dependency from endogenous fatty acids in uninfected cells to exogenous fatty acids in infected macrophages. We demonstrate how quantifiable bioenergetic parameters of the host can be used to accurately measure and track disease, which will enable rapid quantifiable assessment of drug and vaccine efficacy. Our findings uncover new paradigms for understanding the bioenergetic basis of host metabolic reprogramming by Mtb.