title: The EHEC-host interactome reveals novel targets for the translocated intimin receptor.
abstract: Enterohemorrhagic E. coli (EHEC) manipulate their human host through at least 39 effector proteins which hijack host processes through direct protein-protein interactions (PPIs). To identify their protein targets in the host cells, we performed yeast two-hybrid screens, allowing us to find 48 high-confidence protein-protein interactions between 15 EHEC effectors and 47 human host proteins. In comparison to other bacteria and viruses we found that EHEC effectors bind more frequently to hub proteins as well as to proteins that participate in a higher number of protein complexes. The data set includes six new interactions that involve the translocated intimin receptor (TIR), namely HPCAL1, HPCAL4, NCALD, ARRB1, PDE6D, and STK16. We compared these TIR interactions in EHEC and enteropathogenic E. coli (EPEC) and found that five interactions were conserved. Notably, the conserved interactions included those of serine/threonine kinase 16 (STK16), hippocalcin-like 1 (HPCAL1) as well as neurocalcin-delta (NCALD). These proteins co-localize with the infection sites of EPEC. Furthermore, our results suggest putative functions of poorly characterized effectors (EspJ, EspY1). In particular, we observed that EspJ is connected to the microtubule system while EspY1 appears to be involved in apoptosis/cell cycle regulation.
authors.affiliation: Genomics and Proteomics Core Facilities, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Blasche
authors.affiliation: Institute of Molecular Cell Biology, University of Münster, Schlossplatz 5, D-48149 Münster.
authors.forename: Stefan
authors.initials: S
authors.lastname: Arens
authors.affiliation: 1] Joint IRB-BSC Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain [2] Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Via Adamello 16, 20139 Milan - Italy.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Ceol
authors.affiliation: Genomics and Proteomics Core Facilities, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Siszler
authors.affiliation: Institute of Infectiology, ZMBE, University of Münster, Von-Esmarch-Str. 56, D-48149 Münster.
authors.forename: M Alexander
authors.initials: MA
authors.lastname: Schmidt
authors.affiliation: Genomics and Proteomics Core Facilities, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Häuser
authors.affiliation: Genomics and Proteomics Core Facilities, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Schwarz
authors.affiliation: 1] Dept. of Computer Science, Univ. of Miami, 1365 Memorial Drive, Coral Gables, FL 33146, USA [2] Center for Computational Science, Univ. of Miami, 1365 Memorial Drive, Coral Gables, FL 33146, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wuchty
authors.affiliation: 1] Joint IRB-BSC Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain [2] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Patrick
authors.initials: P
authors.lastname: Aloy
authors.affiliation: Center for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, VA 23284, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Uetz
authors.affiliation: 1] Institute of Molecular Cell Biology, University of Münster, Schlossplatz 5, D-48149 Münster [2] Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig.
authors.forename: Theresia
authors.initials: T
authors.lastname: Stradal
authors.affiliation: Genomics and Proteomics Core Facilities, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Koegl
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D054324:Enterohemorrhagic Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D051596:Neurocalcin / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D029968:Escherichia coli Proteins; C497366:EspJ protein, E coli; C520235:HPCAL1 protein, human; C496685:NCALD protein, human; D051596:Neurocalcin; D011956:Receptors, Cell Surface; C109287:Tir protein, E coli; D014157:Transcription Factors; C073819:eaeA protein, E coli; D017346:Protein Serine-Threonine Kinases; C418980:STK16 protein, human