An Ebola, Neisseria and Trypanosoma human protein interaction census reveals a conserved human protein cluster targeted by various human pathogens

Shishir K Gupta; Alicia Ponte-Sucre; Elena Bencurova; Thomas Dandekar

doi:10.1016/j.csbj.2021.09.017

An Ebola, Neisseria and Trypanosoma human protein interaction census reveals a conserved human protein cluster targeted by various human pathogens

Comput Struct Biotechnol J. 2021 Sep 16:19:5292-5308. doi: 10.1016/j.csbj.2021.09.017. eCollection 2021.

Authors

Shishir K Gupta^{1

2}, Alicia Ponte-Sucre^{3

4}, Elena Bencurova¹, Thomas Dandekar^{1

5}

Affiliations

¹ Functional Genomics & Systems Biology Group, Department of Bioinformatics, Biocenter, Am Hubland, University of Würzburg, 97074 Würzburg, Germany.
² Evolutionary Genomics Group, Center for Computational and Theoretical Biology, University of Würzburg, 97078 Würzburg, Germany.
³ Laboratorio de Fisiología Molecular, Instituto de Medicina Experimental, Escuela Luis Razetti, Universidad Central de Venezuela, Caracas, Venezuela.
⁴ Medical Mission Institute, Hermann-Schell-Str. 7, 97074 Würzburg, Germany.
⁵ EMBL Heidelberg, BioComputing Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany.

Abstract

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.

Keywords: Antibiotic targeting; Blood-borne pathogen; DIP, database of interacting proteins; Ebola virus; HLA, human leucocyte antigen; Hub proteins; Human African Trypanosomiasis; Interactome; Life cycle; NM, Neisseria meningitidis; Neisseria meningitidis; PPI, protein–protein interaction; PPIs, protein–protein interactions; Pathway analysis; Protein–protein interaction; Tb, for Trypanosoma brucei;; ZE, for Zaire ebolavirus, Bundibugyo ebolavirus.