Global Analysis of Host and Bacterial Ubiquitinome in Response to Salmonella Typhimurium Infection

Mol Cell. 2016 Jun 16;62(6):967-981. doi: 10.1016/j.molcel.2016.04.015. Epub 2016 May 19.

Abstract

Ubiquitination serves as a critical signal in the host immune response to infection. Many pathogens have evolved strategies to exploit the ubiquitin (Ub) system to promote their own survival through a complex interplay between host defense machinery and bacterial virulence factors. Here we report dynamic changes in the global ubiquitinome of host epithelial cells and invading pathogen in response to Salmonella Typhimurium infection. The most significant alterations in the host ubiquitinome concern components of the actin cytoskeleton, NF-κB and autophagy pathways, and the Ub and RHO GTPase systems. Specifically, infection-induced ubiquitination promotes CDC42 activity and linear ubiquitin chain formation, both being required for NF-κB activation. Conversely, the bacterial ubiquitinome exhibited extensive ubiquitination of various effectors and several outer membrane proteins. Moreover, we reveal that bacterial Ub-modifying enzymes modulate a unique subset of host targets, affecting different stages of Salmonella infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism*
  • Epithelial Cells / metabolism*
  • Epithelial Cells / microbiology
  • HCT116 Cells
  • HeLa Cells
  • Host-Pathogen Interactions
  • Humans
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Proteomics / methods*
  • Salmonella Infections / genetics
  • Salmonella Infections / metabolism*
  • Salmonella typhimurium / metabolism*
  • Salmonella typhimurium / pathogenicity
  • Time Factors
  • Transfection
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination*
  • cdc42 GTP-Binding Protein / metabolism

Substances

  • Bacterial Proteins
  • NF-kappa B
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Protein-Serine-Threonine Kinases
  • TBK1 protein, human
  • I-kappa B Kinase
  • cdc42 GTP-Binding Protein