An Ebola, Neisseria and Trypanosoma human protein interaction census reveals a conserved human protein cluster targeted by various human pathogens.
Comput Struct Biotechnol J
; 19: 5292-5308, 2021.
Article
en En
| MEDLINE
| ID: mdl-34745452
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.
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, proteinprotein interaction; PPIs, proteinprotein interactions; Pathway analysis; Proteinprotein interaction; Tb, for Trypanosoma brucei;; ZE, for Zaire ebolavirus, Bundibugyo ebolavirus
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Comput Struct Biotechnol J
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania