Metabolomics reveals that the cAMP receptor protein regulates nitrogen and peptidoglycan synthesis in Mycobacterium tuberculosis,RSC Advances

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Metabolomics reveals that the cAMP receptor protein regulates nitrogen and peptidoglycan synthesis in Mycobacterium tuberculosis
RSC Advances ( IF 3.9 ) Pub Date : 2020-7-10 , DOI: 10.1039/d0ra05153e
Yi Liu ₁ , Sonia Rebollo-Ramirez ₁ , Gerald Larrouy-Maumus ₁

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Mycobacterium tuberculosis requires extensive sensing and response to environment for its successful survival and pathogenesis, and signalling by cyclic adenosine 3′,5′-monophosphate (cAMP) is an important mechanism. cAMP regulates expression of target genes via interaction with downstream proteins, one of which is cAMP receptor protein (CRP), a global transcriptional regulator. Previous genomic works had identified regulon of CRP and investigated transcriptional changes in crp deletion mutant, however a link to downstream metabolomic events were lacking, which would help better understand roles of CRP. This work aims at investigating changes at metabolome level in M. tuberculosis crp deletion mutant combining untargeted LC-MS analysis and ¹³C isotope tracing analysis. The results were compared with previously published RNA sequencing data. We identified increasing abundances of metabolites related to nitrogen metabolism including ornithine, citrulline and glutamate derivatives, while ¹³C isotope labelling analysis further showed changes in turnover of these metabolites and amino acids, suggesting regulatory roles of CRP in nitrogen metabolism. Upregulation of diaminopimelic acid and its related genes also suggested role of CRP in regulation of peptidoglycan synthesis. This study provides insights on metabolomic aspects of cAMP-CRP regulatory pathway in M. tuberculosis and links to previously published transcriptomic data drawing a more complete map.

中文翻译：

代谢组学揭示 cAMP 受体蛋白调节结核分枝杆菌中氮和肽聚糖的合成

结核分枝杆菌需要对环境进行广泛的感知和响应才能成功生存和发病，而环腺苷 3',5'-单磷酸 (cAMP) 信号传导是一个重要机制。 cAMP通过与下游蛋白相互作用来调节靶基因的表达，其中之一是 cAMP 受体蛋白 (CRP)，它是一种全局转录调节因子。之前的基因组工作已经鉴定了 CRP 的调节子，并研究了crp缺失突变体的转录变化，但缺乏与下游代谢组事件的联系，这将有助于更好地了解 CRP 的作用。本工作旨在结合非靶向 LC-MS 分析和¹³ C 同位素示踪分析，研究结核分枝杆菌 crp缺失突变体代谢组水平的变化。结果与之前发表的 RNA 测序数据进行了比较。我们发现与氮代谢相关的代谢物的丰度不断增加，包括鸟氨酸、瓜氨酸和谷氨酸衍生物，而¹³ C 同位素标记分析进一步显示这些代谢物和氨基酸周转的变化，表明 CRP 在氮代谢中的调节作用。二氨基庚二酸及其相关基因的上调也表明 CRP 在调节肽聚糖合成中的作用。这项研究提供了关于结核分枝杆菌中 cAMP-CRP 调节途径代谢组学方面的见解，并链接到先前发表的转录组数据，绘制了更完整的图谱。

更新日期：2020-07-10

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