|BEARSON S, M|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 4/29/2007
Publication Date: 6/2/2007
Citation: Tuggle, C.K., Wang, Y.F., Couture, O.P., Qu, L., Uthe, J.J., Kuhar, D.J., Lunney, J.K., Nettleton, D., Dekkers, J.C., Bearson S, M.D. 2007. Characterizing the porcine transcriptional regulatory response to infection by Salmonella: identifying putative new NFkB direct targets through comparative bioinformatics.
Technical Abstract: We have collected data on host response to infection from RNA prepared from mesenteric lymph node of swine infected with either Salmonella enterica serovar Typhimurium (ST) or S. Choleraesuis (SC) using the porcine Affymetrix GeneChip. We identified 848 (ST) and 1,853 (SC) genes with statistical evidence for differential expression (DE; p < 0.01, q < 0.26, with fold-change (FC) > 2) in pair-wise comparisons across all infection time-points (0, 8, 24, 48 and 504 hours post-inoculation (hpi)). Comparative annotation and Gene Ontology analyses revealed that a high proportion of up-regulated DE genes in both infections are involved in immune and defense responses. Hierarchical cluster analyses revealed that many genes DE at 24 or 48 hpi are known NFkB targets. Real time gene expression (Q-PCR) confirmed these patterns for 90% of tested NFkB target genes. To further understand this response, we tested the hypothesis that many of the genes in these co-expression clusters are un-recognized direct targets of NFkB. Using a list of genes up-regulated in the SC infection at 8 and/or 24 hpi, we collected orthologous human promoter sequences and used TFM-Explorer to identify a set of 49 gene promoters with statistically significant over-representation of NFkB DNA-binding motifs. Sixteen known NFkB target genes are in this list, indicating the remaining 33 genes are potential novel NFkB targets. Further annotation of these genes, as well as over-representation analysis of other transcription factor motifs, will be performed to increase our understanding of the porcine immune response pathways involved in fighting bacterial infection.