EspH suppresses erk by spatial segregation from CD81 tetraspanin microdomains

Rachana Pattani Ramachandran, Felipe Vences-Catalán, Dan Wiseman, Efrat Zlotkin-Rivkin, Eyal Shteyer, Naomi Melamed-Book, Ilan Rosenshine, Shoshana Levy, Benjamin Aroeti*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Enteropathogenic Escherichia coli (EPEC) belongs to a group of enteric human pathogens known as attaching-and-effacing (A/E) pathogens, which utilize a type III secretion system (T3SS) to translocate a battery of effector proteins from their own cytoplasm into host intestinal epithelial cells. Here we identified EspH to be an effector that prompts the recruitment of the tetraspanin CD81 to infection sites. EspH was also shown to be an effector that suppresses the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (Erk) signaling pathway at longer infection times. The inhibitory effect was abrogated upon deletion of the last 38 amino acids located at the C terminus of the protein. The efficacy of EspHdependent Erk suppression was higher in CD81-deficient cells, suggesting that CD81 may act as a positive regulator of Erk, counteracting Erk suppression by EspH. EspH was found within CD81 microdomains soon after infection but was largely excluded from these domains at a later time. Based on our results, we propose a mechanism whereby CD81 is initially recruited to infection sites in response to EspH translocation. At a later stage, EspH moves out of the CD81 clusters to facilitate effective Erk inhibition. Moreover, EspH selectively inhibits the tumor necrosis factor alpha (TNF- α)-induced Erk signaling pathway. Since Erk and TNF-α have been implicated in innate immunity and cell survival, our studies suggest a novel mechanism by which EPEC suppresses these processes to promote its own colonization and survival in the infected gut.

Original languageAmerican English
Article numbere00303-18
JournalInfection and Immunity
Volume86
Issue number10
DOIs
StatePublished - 1 Oct 2018

Bibliographical note

Publisher Copyright:
Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords

  • Cell membranes
  • Cell polarity
  • Escherichia coli
  • EspH
  • Host-pathogen interactions
  • MAP kinases
  • Type III secretion system

Fingerprint

Dive into the research topics of 'EspH suppresses erk by spatial segregation from CD81 tetraspanin microdomains'. Together they form a unique fingerprint.

Cite this