The EHEC-host interactome reveals novel targets for the translocated intimin receptor

Sci Rep. 2014 Dec 18;4:7531. doi: 10.1038/srep07531.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / metabolism*
  • Enterohemorrhagic Escherichia coli / metabolism*
  • Escherichia coli Proteins / metabolism*
  • Host-Pathogen Interactions / physiology*
  • Humans
  • Neurocalcin / metabolism
  • Protein Interaction Domains and Motifs / physiology*
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptors, Cell Surface / metabolism*
  • Transcription Factors / metabolism

Substances

  • Adhesins, Bacterial
  • Escherichia coli Proteins
  • EspJ protein, E coli
  • HPCAL1 protein, human
  • NCALD protein, human
  • Neurocalcin
  • Receptors, Cell Surface
  • Tir protein, E coli
  • Transcription Factors
  • eaeA protein, E coli
  • Protein-Serine-Threonine Kinases
  • STK16 protein, human