Elucidation of cellular signaling triggered by Francisella infection by comparative phosphoproteomic analysis (981.2)

Abstract

Francisella tularensis is a facultative intracellular bacterium that causes the deadly disease tularemia. Most evidence suggests that Francisella is not well recognized by the innate immune response that normally leads to protection against the infection. To elucidate the cellular signaling underlying this muted recognition of Francisella by the innate immune system, we performed a large‐scale comparative phosphoproteomic analysis of RAW 264.7 cells infected with either Francisella tularensis novicida or Salmonella Typhimurium, which is well recognized by the innate immune system. From our phosphoproteomics analysis >3000 phosphopeptides from >1200 phosphoproteins were identified, of which 368, 169, and 332 phosphopeptides were differentially abundant comparing Francisella‐ or Salmonella‐ infected and control cells at 0, 1, or 4 h post‐infection, respectively. Striking differences in phosphorylation levels on proteins from a diversity of cellular pathways were observed comparing Francisella and Salmonella infections, including key players of the innate immune response, such as AKT and MAP kinases and E3 ubiquitin ligases. In conclusion, our comparative phosphoproteomic analysis of cells infected with Francisella and Salmonella shows differences between the cellular signaling triggered by either pathogen, which may be reflective of specific mechanisms to evade the host immune response. Grant Funding Source: Supported by GM094623 and 8 P41 GM103493‐10