Gupta Shishir K, Ponte-Sucre Alicia, Bencurova Elena, Dandekar Thomas
Functional Genomics & Systems Biology Group, Department of Bioinformatics, Biocenter, Am Hubland, University of Würzburg, 97074 Würzburg, Germany.
Evolutionary Genomics Group, Center for Computational and Theoretical Biology, University of Würzburg, 97078 Würzburg, Germany.
Comput Struct Biotechnol J. 2021 Sep 16;19:5292-5308. doi: 10.1016/j.csbj.2021.09.017. eCollection 2021.
(ZE; , Bundibugyo ebolavirus), (NM), and (Tb) are serious infectious pathogens, spanning viruses, bacteria and protists and all may target the blood and central nervous system during their life cycle. NM and Tb are extracellular pathogens while ZE is obligatory intracellular, targetting immune privileged sites. By using interactomics and comparative evolutionary analysis we studied whether conserved human proteins are targeted by these pathogens. We examined 2797 unique pathogen-targeted human proteins. The information derived from orthology searches of experimentally validated protein-protein interactions (PPIs) resulted both in unique and shared PPIs for each pathogen. Comparing and analyzing conserved and pathogen-specific infection pathways for NM, TB and ZE, we identified human proteins predicted to be targeted in at least two of the compared host-pathogen networks. However, four proteins were common to all three host-pathogen interactomes: the elongation factor 1-alpha 1 (EEF1A1), the SWI/SNF complex subunit SMARCC2 (matrix-associated actin-dependent regulator of chromatin subfamily C), the dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 1 (RPN1), and the tubulin beta-5 chain (TUBB). These four human proteins all are also involved in cytoskeleton and its regulation and are often addressed by various human pathogens. Specifically, we found (i) 56 human pathogenic bacteria and viruses that target these four proteins, (ii) the well researched new pandemic pathogen SARS-CoV-2 targets two of these four human proteins and (iii) nine human pathogenic fungi (yet another evolutionary distant organism group) target three of the conserved proteins by 130 high confidence interactions.
邦迪布焦埃博拉病毒（ZE）、结核分枝杆菌（NM）和锥虫（Tb）是严重的传染性病原体，涵盖病毒、细菌和原生生物，并且在其生命周期中都可能靶向血液和中枢神经系统。NM和Tb是细胞外病原体，而ZE是专性细胞内病原体，靶向免疫特惠部位。通过使用相互作用组学和比较进化分析，我们研究了这些病原体是否靶向保守的人类蛋白质。我们检查了2797种独特的病原体靶向人类蛋白质。从经过实验验证的蛋白质-蛋白质相互作用（PPI）的直系同源搜索中获得的信息产生了每种病原体独特的和共有的PPI。通过比较和分析NM、TB和ZE保守的和病原体特异性的感染途径，我们鉴定出在至少两个比较的宿主-病原体网络中预测会被靶向的人类蛋白质。然而，有四种蛋白质在所有三个宿主-病原体相互作用组中都存在：延伸因子1-α1（EEF1A1）、SWI/SNF复合体亚基SMARCC2（染色质亚家族C的基质相关肌动蛋白依赖性调节剂）、多萜醇二磷酸寡糖-蛋白质糖基转移酶亚基1（RPN1）和微管蛋白β-5链（TUBB）。这四种人类蛋白质都参与细胞骨架及其调节，并且经常被各种人类病原体所作用。具体而言，我们发现：（i）有56种人类致病细菌和病毒靶向这四种蛋白质；（ii）经过充分研究的新型大流行性病原体严重急性呼吸综合征冠状病毒2（SARS-CoV-2）靶向这四种人类蛋白质中的两种；（iii）九种人类致病真菌（另一个进化距离较远的生物体组）通过130种高可信度相互作用靶向其中三种保守蛋白质。
