Salmonella regulation of intestinal stem cells through the Wnt/beta-catenin pathway

FEBS Lett. 2010 Mar 5;584(5):911-6. doi: 10.1016/j.febslet.2010.01.024. Epub 2010 Jan 19.

Abstract

Recent studies have revealed that bacteria target stem cells for long-term survival in a Drosophila model. However, in mammalian models, little is known about bacterial infection and intestinal stem cells. Our study aims at understanding bacterial regulation of the intestinal stem cell in a Salmonella colitis mouse model. We found that Salmonella activates the Wnt/beta-catenin signaling pathway that is known to regulate stem cells. We identified Salmonella protein AvrA that modulates Wnt signaling including upregulating Wnt expression, modifying beta-catenin, increasing total beta-catenin expression, and activating Wnt/beta-catenin transcriptional activity in the intestinal epithelial cells. The numbers of stem cells and proliferative cells increased in the intestine infected with Salmonella expressing AvrA. Our study provides insights into bacterial infection and stem cell maintenance.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cell Proliferation
  • Colitis / metabolism
  • Colitis / microbiology
  • Disease Models, Animal
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Female
  • Fluorescent Antibody Technique
  • Immunoblotting
  • Immunohistochemistry
  • Intestines / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Phosphorylation
  • Polymerase Chain Reaction
  • Salmonella typhimurium / metabolism
  • Salmonella typhimurium / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Stem Cells / microbiology
  • Wnt Proteins / genetics*
  • Wnt Proteins / metabolism*
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • AvrA protein, Salmonella typhimurium
  • Bacterial Proteins
  • Wnt Proteins
  • beta Catenin