Filovirus ebolavirus (ZE; Zaire ebolavirus, Bundibugyo ebolavirus), Neisseria meningitidis (NM), and Trypanosoma brucei (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.

埃博拉丝状病毒（ZE；扎伊尔埃博拉病毒、本迪布焦埃博拉病毒）、脑膜炎奈瑟菌(NM) 和布氏锥虫(Tb) 是严重的传染性病原体，涵盖病毒、细菌和原生生物，所有病毒在其生命周期中都可能以血液和中枢神经系统为目标。NM 和 Tb 是细胞外病原体，而 ZE 是必需的细胞内病原体，针对免疫特权位点。通过使用相互作用组学和比较进化分析，我们研究了保守的人类蛋白质是否是这些病原体的目标。我们检测了 2797 种独特的针对病原体的人类蛋白质。从经过实验验证的蛋白质-蛋白质相互作用 (PPI) 的同源搜索中获得的信息产生了每种病原体的独特和共享的 PPI。通过比较和分析 NM、TB 和 ZE 的保守和病原体特异性感染途径，我们确定了预计在至少两个所比较的宿主-病原体网络中作为目标的人类蛋白质。然而，四种蛋白质是所有三种宿主-病原体相互作用组所共有的：延伸因子 1-α 1 (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因子）、多油酰二磷酸寡糖--蛋白质糖基转移酶亚基 1 (RPN1) 和微管蛋白 beta-5 链 (TUBB)。这四种人类蛋白质也都参与细胞骨架及其调节，并且经常被各种人类病原体所攻击。具体来说，我们发现 (i) 56 种人类致病细菌和病毒以这四种蛋白质为目标，(ii) 经过充分研究的新型大流行病原体 SARS-CoV-2 以这四种人类蛋白质中的两种为目标，以及 (iii) 九种人类致病真菌（尚未得到证实）。另一个进化遥远的有机体群体）通过 130 个高置信度相互作用靶向三个保守蛋白质。