Metabolic flux reprogramming in Mycobacterium tuberculosis-infected human macrophages.
Metabolic flux reprogramming in Mycobacterium tuberculosis-infected human macrophages.
复制标题
结核分枝杆菌感染的人巨噬细胞代谢通量重编程。
DOI：
10.3389/fmicb.2023.1289987
复制
发表时间：
2023
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
代谢通量是任何生命系统新陈代谢和生长的核心。在结核病 (TB) 感染期间，致病性结核分枝杆菌 (Mtb) 会调整其营养行为和代谢通量，以在人类巨噬细胞中生存并引起感染。受感染的宿主细胞也会发生代谢变化。然而，我们对受感染宿主代谢和重编程代谢流节点识别的了解仍然有限。在这项研究中，我们应用基于系统的 13C 代谢通量分析 (MFA) 来测量 Mtb 感染的人类 THP-1 巨噬细胞的细胞内碳代谢通量。我们提供了受感染巨噬细胞的通量图，该图量化了与未感染的巨噬细胞相比，通过糖酵解流向丙酮酸合成显着增加的通量和减少的戊糖磷酸途径通量。三羧酸（TCA）循环通量相对较低，并且氨基酸通量在 Mtb 感染后被重新编程。从我们的工作中获得的宿主代谢通量谱的知识扩展了宿主细胞如何调整其碳代谢以应对结核分枝杆菌感染，并强调了可能为开发新疗法以改善结核病治疗提供目标的重要节点。
Metabolic fluxes are at the heart of metabolism and growth in any living system. During tuberculosis (TB) infection, the pathogenic Mycobacterium tuberculosis (Mtb) adapts its nutritional behaviour and metabolic fluxes to survive in human macrophages and cause infection. The infected host cells also undergo metabolic changes. However, our knowledge of the infected host metabolism and identification of the reprogrammed metabolic flux nodes remains limited. In this study, we applied systems-based 13C-metabolic flux analysis (MFA) to measure intracellular carbon metabolic fluxes in Mtb-infected human THP-1 macrophages. We provide a flux map for infected macrophages that quantified significantly increased fluxes through glycolytic fluxes towards pyruvate synthesis and reduced pentose phosphate pathway fluxes when compared to uninfected macrophages. The tri carboxylic acid (TCA) cycle fluxes were relatively low, and amino acid fluxes were reprogrammed upon Mtb infection. The knowledge of host metabolic flux profiles derived from our work expands on how the host cell adapts its carbon metabolism in response to Mtb infection and highlights important nodes that may provide targets for developing new therapeutics to improve TB treatment.
DOI：
10.3389/fnene.2011.00005
发表时间：
2011
期刊：
Frontiers in neuroenergetics
影响因子：
--
作者：
Amaral AI;Teixeira AP;Håkonsen BI;Sonnewald U;Alves PM
通讯作者：
Alves PM
影响因子：
--
作者：
Duckwall CS;Murphy TA;Young JD
通讯作者：
Young JD