Role of SPI-1 Secreted Effectors in Acute Bovine Response to Salmonella enterica Serovar Typhimurium: A Systems Biology Analysis Approach

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dc.contributorVirginia Techen
dc.contributor.authorLawhon, Sara D.en
dc.contributor.authorKhare, Sangeetaen
dc.contributor.authorRossetti, Carlos A.en
dc.contributor.authorEverts, Robin E.en
dc.contributor.authorGalindo, Cristi L.en
dc.contributor.authorLuciano, Sarah A.en
dc.contributor.authorFigueiredo, Josely F.en
dc.contributor.authorNunes, Jairo E. S.en
dc.contributor.authorGull, Tamaraen
dc.contributor.authorDavidson, George S.en
dc.contributor.authorDrake, Kenneth L.en
dc.contributor.authorGarner, Harold R.en
dc.contributor.authorLewin, Harris A.en
dc.contributor.authorBaumler, Andreas J.en
dc.contributor.authorAdams, Leslie Garryen
dc.date.accessed2014-05-02en
dc.date.accessioned2014-06-17T20:12:07Zen
dc.date.available2014-06-17T20:12:07Zen
dc.date.issued2011-11-11en
dc.description.abstractSalmonella enterica Serovar Typhimurium (S. Typhimurium) causes enterocolitis with diarrhea and polymorphonuclear cell (PMN) influx into the intestinal mucosa in humans and calves. The Salmonella Type III Secretion System (T3SS) encoded at Pathogenicity Island I translocates Salmonella effector proteins SipA, SopA, SopB, SopD, and SopE2 into epithelial cells and is required for induction of diarrhea. These effector proteins act together to induce intestinal fluid secretion and transcription of C-X-C chemokines, recruiting PMNs to the infection site. While individual molecular interactions of the effectors with cultured host cells have been characterized, their combined role in intestinal fluid secretion and inflammation is less understood. We hypothesized that comparison of the bovine intestinal mucosal response to wild type Salmonella and a SipA, SopABDE2 effector mutant relative to uninfected bovine ileum would reveal heretofore unidentified diarrhea-associated host cellular pathways. To determine the coordinated effects of these virulence factors, a bovine ligated ileal loop model was used to measure responses to wild type S. Typhimurium (WT) and a ΔsipA, sopABDE2 mutant (MUT) across 12 hours of infection using a bovine microarray. Data were analyzed using standard microarray analysis and a dynamic Bayesian network modeling approach (DBN). Both analytical methods confirmed increased expression of immune response genes to Salmonella infection and novel gene expression. Gene expression changes mapped to 219 molecular interaction pathways and 1620 gene ontology groups. Bayesian network modeling identified effects of infection on several interrelated signaling pathways including MAPK, Phosphatidylinositol, mTOR, Calcium, Toll-like Receptor, CCR3, Wnt, TGF-β, and Regulation of Actin Cytoskeleton and Apoptosis that were used to model of host-pathogen interactions. Comparison of WT and MUT demonstrated significantly different patterns of host response at early time points of infection (15 minutes, 30 minutes and one hour) within phosphatidylinositol, CCR3, Wnt, and TGF-β signaling pathways and the regulation of actin cytoskeleton pathway.en
dc.description.sponsorshipThis work was funded by grants to AJB and LGA from the National Institute of Allergy and Infectious Disease (1 R01 A144170-01-A1, 1 R01 AI076246 01-A2 and USDA 2002-35204-12247). Additionally, SDL received support from the Public Health Service Grant (AI060933). The funders had no role in study design, data collection and analysis, decision ten
dc.identifier.citationLawhon SD, Khare S, Rossetti CA, Everts RE, Galindo CL, et al. (2011) Role of SPI-1 Secreted Effectors in Acute Bovine Response to Salmonella enterica Serovar Typhimurium: A Systems Biology Analysis Approach. PLoS ONE 6(11): e26869. doi:10.1371/journal.pone.0026869en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0026869en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://hdl.handle.net/10919/48988en
dc.identifier.urlhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0026869en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectBayes theoremen
dc.subjectBovineen
dc.subjectGene expressionen
dc.subjectMicroarraysen
dc.subjectSalmonellaen
dc.subjectSalmonellosien
dc.subjectWnt signaling cascadeen
dc.titleRole of SPI-1 Secreted Effectors in Acute Bovine Response to Salmonella enterica Serovar Typhimurium: A Systems Biology Analysis Approachen
dc.title.serialPLoS ONEen
dc.typeArticle - Refereeden

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