Metabolomics of Mycobacterium tuberculosis Reveals Compartmentalized Co-Catabolism of Carbon Substrates
Metabolomics of Mycobacterium tuberculosis Reveals Compartmentalized Co-Catabolism of Carbon Substrates
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DOI：
10.1016/j.chembiol.2010.08.009
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发表时间：
2010-10-29
影响因子：
--
通讯作者：
Rhee, Kyu Y.
中科院分区：
文献类型：
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作者：
de Carvalho, Luiz Pedro S.;Fischer, Steven M.;Rhee, Kyu Y.
对宿主环境的代谢适应是结核分枝杆菌（Mycobacterium tuberculosis，Mtb）致病性的一个决定性特征，但我们缺乏对其代谢网络的生化知识许多细菌利用分解代谢物阻遏作为调节机制，通过以优选顺序消耗单个碳底物并以二次动力学生长来最大化生长，令人惊讶的是，在C-13标记的碳底物上生长的Mtb的非靶向代谢物谱显示Mtb可以同时分解代谢多种碳源以实现增强的双相生长。此外，当共分解代谢多种碳源时，结核分枝杆菌通过糖酵解、戊糖磷酸和/或三羧酸途径对每种碳源进行差异性分解代谢，以获得不同的代谢命运。这种细菌中间代谢的不寻常拓扑组织以前未观察到，可能有助于结核分枝杆菌的致病性。
Metabolic adaptation to the host environment is a defining feature of the pathogenicity of Mycobacterium tuberculosis (Mtb), but we lack biochemical knowledge of its metabolic networks Many bacteria use catabolite repression as a regulatory mechanism to maximize growth by consuming individual carbon substrates in a preferred sequence and growing with diauxic kinetics Surprisingly, untargeted metabolite profiling of Mtb growing on C-13-labeled carbon substrates revealed that Mtb could catabolize multiple carbon sources simultaneously to achieve enhanced monophasic growth Moreover, when co-catabolizing multiple carbon sources, Mtb differentially catabolized each carbon source through the glycolytic, pentose phosphate, and/or tricarboxylic acid pathways to distinct metabolic fates This unusual topologic organization of bacterial intermediary metabolism has not been previously observed and may subserve the pathogenicity of Mtb