The Salmonella Effector AvrA Mediates Bacterial Intracellular Survival During Infection in Vivo

Cell Microbiol. 2012 Jan;14(1):28-39. doi: 10.1111/j.1462-5822.2011.01694.x. Epub 2011 Sep 28.


The enteric pathogen Salmonella typhimurium secretes the preformed AvrA effector protein into host cells. This acetyltransferase has been shown to modulate mammalian intestinal immune and survival responses by inhibition of JNK MAPK. To study the role of this effector in natural enteric infection, we used a mouse model to compare wild-type S. typhimurium to an isogenic AvrA null Salmonella mutant. Salmonella lacking AvrA induced increased intestinal inflammation, more intense systemic cytokine responses, and increased apoptosis in epithelial cells. Increased apoptosis was also observed in extra epithelial macrophages. AvrA null-infected mice consistently showed higher bacterial burden within mucosal lymphoid tissues, spleen and liver by 5 days post infection, which indicated a more severe clinical course. To study the molecular mechanisms involved, recombinant adenoviruses expressing AvrA or mutant AvrA proteins were constructed, which showed appropriate expression and mediated the expected inhibition of JNK signalling. Cultured epithelial cells and macrophages transduced with AvrA expressing adenovirus were protected from apoptosis induced by exogenous stimuli. In conclusion, the results demonstrated that Salmonella AvrA modulates survival of infected macrophages likely via JNK suppression, and prevents macrophage death and rapid bacterial dissemination. AvrA suppression of apoptosis in infected macrophages may allow for establishment of a stable intracellular niche typical of intracellular pathogens.

Publication types

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

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Apoptosis / immunology*
  • Bacterial Load
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Line
  • Cytokines / metabolism
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Female
  • Intestinal Mucosa / metabolism
  • Intestines / immunology
  • Intestines / microbiology
  • Lymphoid Tissue / microbiology
  • MAP Kinase Signaling System / genetics
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Salmonella Infections / immunology*
  • Salmonella Infections / metabolism
  • Salmonella Infections / pathology
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / immunology
  • Salmonella typhimurium / metabolism


  • AvrA protein, Salmonella typhimurium
  • Bacterial Proteins
  • Cytokines