Global metabolomic analysis of a mammalian host infected with Bacillus anthracis.
Global metabolomic analysis of a mammalian host infected with Bacillus anthracis.
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感染炭疽杆菌的哺乳动物宿主的整体代谢组学分析。
DOI：
10.1128/iai.00947-15
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发表时间：
2015
影响因子：
3.1
通讯作者：
Maresso,AnthonyW
中科院分区：
文献类型：
--
作者：
Nguyen,ChinhTQ;Shetty,Vivekananda;Maresso,AnthonyW
DNA提供设计生命的信息，蛋白质提供构建生命的材料，而代谢组可以被视为为生命提供动力的生理机能。因此，代谢组学这个负责研究因生物变化而产生的动态小分子波动的领域，现在正被用于研究疾病的基础。在这里，我们描述了一个全面的代谢组学分析的系统性细菌感染使用炭疽杆菌，炭疽病的病原，作为模型病原体。一项器官和血液分析发现，炭疽杆菌抑制了大约400种代谢物，包括几种与炎症有关的关键脂质。早在感染后1天就检测到代谢物变化，远早于疾病发作或细菌向器官扩散，这证明了该方法的敏感性。利用药理抑制宿主磷脂酶的功能研究支持了这些关键酶和脂质介质在炭疽病期间宿主存活中的作用。最后，将结果整合起来，提供炭疽芽胞杆菌如何改变宿主生理的全面图景。总的来说，本研究的结果为使用代谢组学作为识别和研究影响感染结果的新型宿主-病原体相互作用的平台提供了蓝图。
Whereas DNA provides the information to design life and proteins provide the materials to construct it, the metabolome can be viewed as the physiology that powers it. As such, metabolomics, the field charged with the study of the dynamic small-molecule fluctuations that occur in response to changing biology, is now being used to study the basis of disease. Here, we describe a comprehensive metabolomic analysis of a systemic bacterial infection using Bacillus anthracis, the etiological agent of anthrax disease, as the model pathogen. An organ and blood analysis identified approximately 400 metabolites, including several key classes of lipids involved in inflammation, as being suppressed by B. anthracis. Metabolite changes were detected as early as 1 day postinfection, well before the onset of disease or the spread of bacteria to organs, which testifies to the sensitivity of this methodology. Functional studies using pharmacologic inhibition of host phospholipases support the idea of a role of these key enzymes and lipid mediators in host survival during anthrax disease. Finally, the results are integrated to provide a comprehensive picture of how B. anthracis alters host physiology. Collectively, the results of this study provide a blueprint for using metabolomics as a platform to identify and study novel host-pathogen interactions that shape the outcome of an infection.