Genome-wide Analysis of the Host Intracellular Network that Regulates Survival of Mycobacterium tuberculosis
Genome-wide Analysis of the Host Intracellular Network that Regulates Survival of Mycobacterium tuberculosis
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DOI：
10.1016/j.cell.2010.02.012
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发表时间：
2010-03-05
期刊：
影响因子：
64.5
通讯作者：
Rao, Kanury V. S.
中科院分区：
文献类型：
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作者：
Kumar, Dhiraj;Nath, Lekha;Rao, Kanury V. S.
我们进行了全基因组的小干扰RNA（siRNA）筛选，以鉴定在感染了结核分枝杆菌强毒株的人类巨噬细胞中调控病原体负荷的宿主因子。经过反复的确认以及验证，鉴定出275个此类分子，发现它们通过密集的相互作用网络在功能上相互关联。这个网络进而对被病原体激活和干扰的宿主细胞功能模块进行了分子层面的描述。重要的是，针对一组现场分离株的二次筛选显示，宿主界面的分子组成随病原体的基因型和表型特性而变化。然而，对这些差异的分析使得能够鉴定出那些无论病原体所采用的适应机制如何多样化都始终参与其中的宿主因子。有趣的是，发现这些因子主要通过调控自噬发挥作用。
We performed a genome-wide siRNA screen to identify host factors that regulated pathogen load in human macrophages infected with a virulent strain of Mycobacterium tuberculosis. Iterative rounds of confirmation, followed by validation, identified 275 such molecules that were all found to functionally associate with each other through a dense network of interactions. This network then yielded to a molecular description of the host cell functional modules that were both engaged and perturbed by the pathogen. Importantly, a subscreen against a panel of field isolates revealed that the molecular composition of the host interface varied with both genotype and the phenotypic properties of the pathogen. An analysis of these differences, however, permitted identification of those host factors that were invariantly involved, regardless of the diversification in adaptive mechanisms employed by the pathogen. Interestingly, these factors were found to predominantly function through the regulation of autophagy.