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

BMC Microbiology

Research Article

Yinglin Xia¹  Rong Lu²  Xingyin Liu²  Shaoping Wu²  Jun Sun³ 

[1] Department of Biostatistics and Computational Biology, University of Rochester, 601 Elmwood Avenue, 14642, Rochester, NY, USA;Department of Medicine, Gastroenterology & Hepatology Division, University of Rochester, 601 Elmwood Avenue, 14642, Rochester, NY, USA;Department of Medicine, Gastroenterology & Hepatology Division, University of Rochester, 601 Elmwood Avenue, 14642, Rochester, NY, USA;Department of Microbiology and Immunology, University of Rochester, 601 Elmwood Avenue, 14642, Rochester, NY, USA;Wilmot Cancer Center, University of Rochester, 601 Elmwood Avenue, 14642, Rochester, NY, USA;

关键词: Gene Ontology;    Post Infection;    Ingenuity Pathway Analysis;    Infection Group;    Mouse Colon;   

DOI  :  10.1186/1471-2180-10-326

 received in 2010-02-03, accepted in 2010-12-23,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe 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).ResultsWe 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.ConclusionBoth 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.

【 授权许可】

Unknown   
© Liu et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.