|KOMMADATH, ARUN - University Of Alberta|
|BAO, HUA - University Of Alberta|
|ARANTES, ADRIANO - University Of Alberta|
|PLASTOW, GRAHAM - University Of Alberta|
|TUGGLE, CHRISTOPHER - Iowa State University|
|GUAN, LE LUO - University Of Alberta|
|STOTHARD, PAUL - University Of Alberta|
Submitted to: Biomed Central (BMC) Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/27/2014
Publication Date: 6/9/2014
Citation: Kommadath, A., Bao, H., Arantes, A.S., Plastow, G.S., Tuggle, C.K., Bearson, S.M., Guan, L., Stothard, P. 2014. Gene co-expression network analysis identifies porcine genes associated with variation in Salmonella shedding. Biomed Central (BMC) Genomics. 15(452). Available: http://www.biomedcentral.com/1471-2164/15/452.
Interpretive Summary: Salmonella is the most prevalent human foodborne pathogen in the United States. Salmonella can reside in the gut of food-animals for extended periods of time without causing clinical symptoms. This Salmonella carrier-status poses long term contamination threats throughout the food chain. Thus, implementing Salmonella control strategies at the farm will reduce environmental contamination and concerns associated with antibiotic usage. One potential method of intervention is to select animals with improved genetic resistance to Salmonella. Our research has shown that the expression of specific genes in pigs is related to the amount of Salmonella being shed in the feces of the pigs. In fact, the present study revealed that even before the pigs were exposed to Salmonella, pigs that would ultimately shed lower levels of Salmonella were already expressing immune response genes, compared to the pigs that would shed higher amounts of Salmonella for a longer period or time. Therefore, the expression of immune response genes in the "will-be" low Salmonella-shedder pigs appears to have better prepared the pigs for the Salmonella exposure compared to the "will-be" high Salmonella-shedder pigs. Identifying alterative methods for the control and prevention of Salmonella in food animals (such as genetic improvement) is critical for improved profitability for food-animal producers, reduced antibiotic usage and safer food for consumers.
Technical Abstract: Salmonella enterica serovar Typhimurium is a gram-negative bacterium that can colonize the gut of humans and several species of food producing farm animals to cause enteric or septicaemic salmonellosis. While many studies have looked into the host genetic response to Salmonella infection, relatively few have used correlation of shedding traits to gene expression patterns to identify genes whose variable expression among different individuals may be associated with differences in Salmonella clearance and resistance. Here, we aimed to identify porcine genes and gene co-expression networks that differentiate distinct responses to Salmonella challenge with respect to faecal Salmonella shedding. Results Peripheral blood transcriptome profiles from 16 pigs belonging to extremes of the trait of faecal Salmonella shedding counts recorded up to 20 days post-inoculation (low shedders (LS), n=8; persistent shedders (PS), n=8) were generated using RNA-sequencing from samples collected just before (day 0) and two days after (day 2) Salmonella inoculation. Weighted gene co-expression network analysis of day 0 samples identified four modules of co-expressed genes significantly correlated with Salmonella shedding counts upon future challenge. Two of those modules consisted largely of innate immunity related genes, many of which were significantly up-regulated at day 2 post-inoculation. These modules also differed between LS and PS in network properties such as gene connectivity as well as in mean gene-wise expression levels, both being higher in LS. Genes within these modules include those previously reported to be involved in Salmonella resistance such as SLC11A1 (formerly NRAMP1), TLR4, CD14 and CCR1 and those for which an association with Salmonella is novel, for example, SIGLEC5, IGSF6 and TNFSF13B. Conclusions Our analysis integrates gene co-expression network analysis, gene-trait correlations and differential expression to provide new candidate regulators of Salmonella shedding in pigs. The significantly higher network connectivity and comparatively higher expression of genes within Salmonella shedding associated modules in LS compared to PS even before Salmonella challenge may be factors contributing to the decreased fecal shedding observed in LS following challenge.