Molecular Plant Physiology, Max-Planck-Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
Mol Syst Biol. 2010 May 11;6:364. doi: 10.1038/msb.2010.18.
Environmental fluctuations lead to a rapid adjustment of the physiology of Escherichia coli, necessitating changes on every level of the underlying cellular and molecular network. Thus far, the majority of global analyses of E. coli stress responses have been limited to just one level, gene expression. Here, we incorporate the metabolite composition together with gene expression data to provide a more comprehensive insight on system level stress adjustments by describing detailed time-resolved E. coli response to five different perturbations (cold, heat, oxidative stress, lactose diauxie, and stationary phase). The metabolite response is more specific as compared with the general response observed on the transcript level and is reflected by much higher specificity during the early stress adaptation phase and when comparing the stationary phase response to other perturbations. Despite these differences, the response on both levels still follows the same dynamics and general strategy of energy conservation as reflected by rapid decrease of central carbon metabolism intermediates coinciding with downregulation of genes related to cell growth. Application of co-clustering and canonical correlation analysis on combined metabolite and transcript data identified a number of significant condition-dependent associations between metabolites and transcripts. The results confirm and extend existing models about co-regulation between gene expression and metabolites demonstrating the power of integrated systems oriented analysis.
环境波动导致大肠杆菌的生理学迅速调整，需要对细胞和分子网络的各个层面进行改变。到目前为止，大多数大肠杆菌应激反应的全局分析都仅限于一个层面，即基因表达。在这里，我们将代谢物组成与基因表达数据结合起来，通过描述大肠杆菌对五种不同扰动（冷、热、氧化应激、乳糖双重营养和静止期）的详细时间分辨响应，提供对系统水平应激调整的更全面的了解。与转录水平上观察到的一般响应相比，代谢物响应更具特异性，并且在早期应激适应阶段以及将静止期响应与其他扰动进行比较时，特异性更高。尽管存在这些差异，但两个层面的响应仍然遵循相同的动力学和能量守恒的一般策略，表现为与细胞生长相关的基因下调同时，中心碳代谢中间产物迅速减少。对组合代谢物和转录数据应用共聚类和典型相关分析，确定了代谢物和转录物之间存在大量与条件相关的显著关联。结果证实并扩展了关于基因表达和代谢物之间的共调控的现有模型，展示了面向系统的综合分析的强大功能。
