Metabolite analysis of Mycobacterium species under aerobic and hypoxic conditions reveals common metabolic traits.
Metabolite analysis of Mycobacterium species under aerobic and hypoxic conditions reveals common metabolic traits.
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DOI：
10.1099/mic.0.000325
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发表时间：
2016-08
期刊：
影响因子：
1.5
通讯作者：
M. Drapal;P. Wheeler;P. Fraser
中科院分区：
文献类型：
--
作者：
M. Drapal;P. Wheeler;P. Fraser
已经采用代谢物分析方法来阐明五种分枝杆菌（两种快速生长和三种缓慢生长）在设定培养条件下的代谢适应，这些菌株有可能作为结核分枝杆菌（Mtb）的模型生物。在指定的生长阶段和 Mtb 在感染期间经历的代表性环境（营养和氧气消耗）下进行了分析。该程序可用于测定一系列代谢物（60-120 种化合物），包括核苷酸、氨基酸、有机酸、糖类、脂肪酸、甘油、酯、磷酸酯和类异戊二烯。在这些类别的化合物中，确定了关键的生物标志物代谢物，它们可以作为途径/过程活性的指标。在许多情况下，在整个实验条件下观察到所有五个物种的共同代谢物特征（例如尿嘧啶表明 DNA 修复）。氨基酸含量，尤其是谷氨酸，凸显了所研究的快速和缓慢生长的分枝杆菌之间的不同特性（例如氮同化）。在缺氧条件下，快速生长和缓慢生长的分枝杆菌代谢物组成的最大相似性是显而易见的。与之前报道的转录组数据的比较显示转录变化和代谢物含量之间存在很强的相关性。总的来说，这些数据验证了代谢物水平上转录的变化，表明转录是分枝杆菌细胞调节的主要模式之一。代谢物和转录之间相关性有限的领域（例如缺氧培养）值得进一步研究，以阐明和利用转录后调控模式。所使用的实验室条件与来自体内条件的数据之间的强相关性表明所应用的方法对于我们对这些分枝杆菌物种的细胞调节的理解是有价值的补充。
A metabolite profiling approach has been implemented to elucidate metabolic adaptation at set culture conditions in five Mycobacterium species (two fast- and three slow-growing) with the potential to act as model organisms for Mycobacterium tuberculosis (Mtb). Analysis has been performed over designated growth phases and under representative environments (nutrient and oxygen depletion) experienced by Mtb during infection. The procedure was useful in determining a range of metabolites (60-120 compounds) covering nucleotides, amino acids, organic acids, saccharides, fatty acids, glycerols, -esters, -phosphates and isoprenoids. Among these classes of compounds, key biomarker metabolites, which can act as indicators of pathway/process activity, were identified. In numerous cases, common metabolite traits were observed for all five species across the experimental conditions (e.g. uracil indicating DNA repair). Amino acid content, especially glutamic acid, highlighted the different properties between the fast- and slow-growing mycobacteria studied (e.g. nitrogen assimilation). The greatest similarities in metabolite composition between fast- and slow-growing mycobacteria were apparent under hypoxic conditions. A comparison to previously reported transcriptomic data revealed a strong correlation between changes in transcription and metabolite content. Collectively, these data validate the changes in the transcription at the metabolite level, suggesting transcription exists as one of the predominant modes of cellular regulation in Mycobacterium. Sectors with restricted correlation between metabolites and transcription (e.g. hypoxic cultivation) warrant further study to elucidate and exploit post-transcriptional modes of regulation. The strong correlation between the laboratory conditions used and data derived from in vivo conditions, indicate that the approach applied is a valuable addition to our understanding of cell regulation in these Mycobacterium species.