Selective inhibition of type III secretion activated signaling by the Salmonella effector AvrA

PLoS Pathog. 2009 Sep;5(9):e1000595. doi: 10.1371/journal.ppat.1000595. Epub 2009 Sep 25.

Abstract

Salmonella enterica utilizes a type III secretion system (TTSS) encoded in its pathogenicity island 1 to mediate its initial interactions with intestinal epithelial cells, which are characterized by the stimulation of actin cytoskeleton reorganization and a profound reprogramming of gene expression. These responses result from the stimulation of Rho-family GTPases and downstream signaling pathways by specific effector proteins delivered by this TTSS. We show here that AvrA, an effector protein of this TTSS, specifically inhibits the Salmonella-induced activation of the JNK pathway through its interaction with MKK7, although it does not interfere with the bacterial infection-induced NF-kappaB activation. We also show that AvrA is phosphorylated at evolutionary conserved residues by a TTSS-effector-activated ERK pathway. This interplay between effector proteins delivered by the same TTSS highlights the remarkable complexity of these systems.

Publication types

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

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / physiology*
  • Cell Line
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Kinase 7 / metabolism
  • Mutation
  • NF-kappa B / metabolism
  • Phosphorylation
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Salmonella Infections / metabolism
  • Salmonella Infections / microbiology*
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism
  • Salmonella typhimurium / pathogenicity
  • Salmonella typhimurium / physiology*
  • Secretory Pathway
  • Signal Transduction
  • Two-Hybrid System Techniques

Substances

  • AvrA protein, Salmonella enterica
  • Bacterial Proteins
  • NF-kappa B
  • Spi1 protein, Salmonella
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 7
  • MAP2K7 protein, human