A mixed nitrogen diet and compartmentalized utilization for Mycobacterium tuberculosis replicating in host cells: results of a systems-based analysis
A mixed nitrogen diet and compartmentalized utilization for Mycobacterium tuberculosis replicating in host cells: results of a systems-based analysis
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混合氮饮食和结核分枝杆菌在宿主细胞中复制的分区利用：基于系统的分析结果
DOI：
10.1101/542480
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Borah K
中科院分区：
文献类型：
--
作者：
Borah K
结核分枝杆菌（Mycobacterium tuberculosis，Mtb）的氮代谢对于该病原体在宿主巨噬细胞内的存活和毒力至关重要，但对从宿主获得的氮源及其同化途径知之甚少。在这里，我们进行了基于系统的分析胞内结核分枝杆菌的氮代谢，并开发了15 N-通量光谱比分析（FSRA），以探测宿主细胞和结核分枝杆菌之间的代谢串扰。我们证明，细胞内结核分枝杆菌获得氮从多个氨基酸的巨噬细胞，包括谷氨酸，谷氨酰胺，天冬氨酸，丙氨酸，甘氨酸和缬氨酸，谷氨酰胺是主要的氮供体。每种氮源都被独特地同化到特定的细胞内库中，这表明代谢是区室化的。在体外培养的结核分枝杆菌中没有观察到这一点，表明当病原体进入细胞内环境时，氮代谢发生了转变。这些结果为开发创新的抗结核疗法提供了潜在的代谢靶点的线索。
Nitrogen metabolism of Mycobacterium tuberculosis (Mtb) is crucial for the survival and virulence of this pathogen inside host macrophages but little is known about the nitrogen sources acquired from the host or their route of assimilation. Here we performed a systems-based analysis of nitrogen metabolism in intracellullar Mtb and developed 15N-Flux Spectral Ratio Analysis (FSRA) to probe the metabolic cross-talk between the host cell and Mtb. We demonstrate that intracellular Mtb acquires nitrogen from multiple amino acids in the macrophage including glutamate, glutamine, aspartate, alanine, glycine and valine, with glutamine being the predominant nitrogen donor. Each nitrogen source is uniquely assimilated into specific intracellular pools indicating compartmentalised metabolism. This was not observed for in vitro-grown Mtb indicating that there is a switch in nitrogen metabolism when the pathogen enters the intracellular environment. These results provide clues about the potential metabolic targets for development of innovative anti-tuberculosis therapies.
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影响因子：
3.1
作者：
Sampson, SL;Dascher, CC;Hondalus, MK
通讯作者：
Hondalus, MK
影响因子：
4
作者：
Amorim Franco TM;Favrot L;Vergnolle O;Blanchard JS
通讯作者：
Blanchard JS
13C 代谢通量分析确定了分枝杆菌中丙酮酸异化的不寻常途径，需要异柠檬酸裂解酶和二氧化碳固定
影响因子：
6.7
作者：
D. Beste;B. Bonde;Nathaniel D. Hawkins;J. Ward;M. H. Beale;S. Noack;Katharina Nö;N. Kruger;R. Ratcliffe;J. McFadden;Eric J. Rubin
通讯作者：
Eric J. Rubin
影响因子：
3.1
作者：
Gouzy, Alexandre;Poquet, Yannick;Neyrolles, Olivier
通讯作者：
Neyrolles, Olivier
DOI：
10.1107/s1744309109036690
发表时间：
2009-11
期刊：
Acta crystallographica. Section F, Structural biology and crystallization communications
影响因子：
--
作者：
L. Tremblay;J. Blanchard
通讯作者：
L. Tremblay;J. Blanchard