Centrality in the host-pathogen interactome is associated with pathogen fitness during infection.
Centrality in the host-pathogen interactome is associated with pathogen fitness during infection.
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DOI：
10.1038/ncomms14092
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发表时间：
2017-01-16
影响因子：
16.6
通讯作者：
Torrent Burgas M
中科院分区：
文献类型：
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作者：
Crua Asensio N;Muñoz Giner E;de Groot NS;Torrent Burgas M
为了发挥其功能，蛋白质必须相互作用，但这些相互作用如何影响细菌感染仍然难以捉摸。在这里，我们证明宿主-病原体相互作用组中的连接性与感染期间病原体的适应性直接相关。使用鼠疫耶尔森氏菌作为模型生物，我们表明中心性-致死性规则适用于感染期间的病原体适应性，但仅当考虑宿主-病原体相互作用组时。我们的结果表明，病原体蛋白在感染过程中的重要性与其与宿主相互作用的次数直接相关。我们还表明，引起宿主相互作用组广泛重新布线的病原体蛋白对感染期间病原体的适应性具有更大的影响。因此，我们的结论是，宿主-病原体相互作用组中的中心应该被探索作为抗菌药物设计的有希望的目标。枢纽对于生物体内蛋白质网络的功能至关重要。在这里，作者表明，在感染过程中，鼠疫耶尔森氏菌宿主-病原体相互作用组中具有高度中心性的蛋白质对于感染期间病原体的适应性最为重要，并强调了可能导致宿主相互作用组显着扰动的病原体蛋白质的重要性。
To perform their functions proteins must interact with each other, but how these interactions influence bacterial infection remains elusive. Here we demonstrate that connectivity in the host–pathogen interactome is directly related to pathogen fitness during infection. Using Y. pestis as a model organism, we show that the centrality-lethality rule holds for pathogen fitness during infection but only when the host–pathogen interactome is considered. Our results suggest that the importance of pathogen proteins during infection is directly related to their number of interactions with the host. We also show that pathogen proteins causing an extensive rewiring of the host interactome have a higher impact in pathogen fitness during infection. Hence, we conclude that hubs in the host–pathogen interactome should be explored as promising targets for antimicrobial drug design. Hubs tend to be essential for function in protein networks within organisms. Here, the authors show that during infection, it is the proteins with high centrality in the Y. pestis host–pathogen interactome that are most important for pathogen fitness during infection, and highlight the importance of pathogen proteins that likely cause significant perturbation of the host interactome.