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Background  The  Salmonella AvrA  gene is present in 80% of  Salmonella enterica serovar  strains. AvrA protein mimics the activities of some eukaryotic proteins and uses these activities to the pathogen's advantage by debilitating the target cells, such as intestinal epithelial cells. Therefore, it is important to understand how AvrA works in targeting eukaryotic signaling pathways in intestinal infection  in vivo . In this study, we hypothesized that AvrA interacts with multiple stress pathways in eukaryotic cells to manipulate the host defense system. A whole genome approach combined with bioinformatics assays was used to investigate the  in vivo  genetic responses of the mouse colon to  Salmonella  with or without AvrA protein expression in the early stage (8 hours) and late stage (4 days). Specifically, we examined the gene expression profiles in mouse colon as it responded to pathogenic  Salmonella  stain SL1344 (with AvrA expression) or SB1117 (without AvrA expression).    Results  We identified the eukaryotic targets of AvrA and the cell signaling pathways regulated by AvrA  in vivo . We found that pathways, such as mTOR, NF-kappaB, platelet-derived growth factors, vascular endothelial growth factor, oxidative phosphorylation, and mitogen-activated protein kinase signaling are specifically regulated by AvrA  in vivo  and are associated with inflammation, anti-apoptosis, and proliferation. At the early stage of  Salmonella  infection, AvrA mainly targeted pathways related to nuclear receptor signaling and oxidative phosphorylation. At the late stage of  Salmonella  infection, AvrA is associated with interferon-gamma responses.    Conclusion  Both early and late phases of the host response exhibit remarkable specificity for the AvrA+  Salmonella . Our studies provide new insights into the eukaryotic molecular cascade that combats  Salmonella -associated intestinal infection  in vivo .

Eukaryotic signaling pathways targeted by Salmonella effector protein AvrA in intestinal infection in vivo