The human-bacterial pathogen protein interaction networks of Bacillus anthracis, Francisella tularensis, and Yersinia pestis.
The human-bacterial pathogen protein interaction networks of Bacillus anthracis, Francisella tularensis, and Yersinia pestis.
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DOI：
10.1371/journal.pone.0012089
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发表时间：
2010-08-09
期刊：
影响因子：
3.7
通讯作者：
Sobral BW
中科院分区：
文献类型：
--
作者：
Dyer MD;Neff C;Dufford M;Rivera CG;Shattuck D;Bassaganya-Riera J;Murali TM;Sobral BW
炭疽芽孢杆菌、图拉氏方济氏菌和鼠疫耶尔森氏菌分别是引起炭疽、致死性急性肺病和腺鼠疫的细菌性病原体，被列为NIAID A类优先病原体，可能用作生物武器。然而，人类蛋白质和这些细菌中的蛋白质之间的相互作用仍然没有得到很好的描述，导致对它们的发病机制和免疫逃避机制的了解还不完全。在这项研究中，我们使用高通量酵母双杂交试验来鉴定人类蛋白质和来自这三种病原体的蛋白质之间的物理相互作用。从进行的超过25万次筛查中，我们确认了3073例人类B型病毒。炭疽病，1,383人-F。和4,059人Y。鼠疫病毒蛋白-蛋白质相互作用，包括304株炭疽杆菌、52株图拉氏杆菌和330株尚未鉴定的鼠疫杆菌蛋白之间的相互作用。计算分析表明，病原体蛋白优先与人类蛋白质相互作用，而人类蛋白质是人类PPI网络的枢纽和瓶颈。此外，我们计算了在三个网络中保守的人类病原体PPI的模块。在功能上，这些保守的模块揭示了不同病原体如何与参与炎症和免疫的关键宿主途径相互作用的共同点。这些数据构成了为细菌病原体及其人类宿主构建的第一个广泛的蛋白质相互作用网络。这项研究为宿主-病原体的相互作用提供了新的见解。
Bacillus anthracis, Francisella tularensis, and Yersinia pestis are bacterial pathogens that can cause anthrax, lethal acute pneumonic disease, and bubonic plague, respectively, and are listed as NIAID Category A priority pathogens for possible use as biological weapons. However, the interactions between human proteins and proteins in these bacteria remain poorly characterized leading to an incomplete understanding of their pathogenesis and mechanisms of immune evasion. In this study, we used a high-throughput yeast two-hybrid assay to identify physical interactions between human proteins and proteins from each of these three pathogens. From more than 250,000 screens performed, we identified 3,073 human-B. anthracis, 1,383 human-F. tularensis, and 4,059 human-Y. pestis protein-protein interactions including interactions involving 304 B. anthracis, 52 F. tularensis, and 330 Y. pestis proteins that are uncharacterized. Computational analysis revealed that pathogen proteins preferentially interact with human proteins that are hubs and bottlenecks in the human PPI network. In addition, we computed modules of human-pathogen PPIs that are conserved amongst the three networks. Functionally, such conserved modules reveal commonalities between how the different pathogens interact with crucial host pathways involved in inflammation and immunity. These data constitute the first extensive protein interaction networks constructed for bacterial pathogens and their human hosts. This study provides novel insights into host-pathogen interactions.
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