title: Eukaryotic signaling pathways targeted by Salmonella effector protein AvrA in intestinal infection in vivo.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Gastroenterology & Hepatology Division, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Xingyin
authors.initials: X
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Lu
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Xia
authors.forename: Shaoping
authors.initials: S
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D003106:Colon / Q000382:microbiology / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D051379:Mice; D008810:Mice, Inbred C57BL; D012480:Salmonella Infections / Q000382:microbiology / Q000473:pathology*; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C495717:AvrA protein, Salmonella enterica; D001426:Bacterial Proteins