Molecular basis of foodborne disease risk of variants of Salmonella Typhimurium DT193 and U288

Lead Research Organisation: University of Edinburgh
Department Name: The Roslin Institute

Abstract

The bacterium Salmonella accounts for about 125 million incidents of disease worldwide each year, and nearly a million deaths. The morbidity and mortality caused by this pathogen has a significant impact on the economies of both resource rich and resource poor countries. Most cases of non-typhoidal Salmonella are thought to result from fecal contamination of food and food products, either directly in the food chain or by cross contamination in the home or restaurants. A common and therefore critical step for this is the entry of the bacterium into the food chain from livestock and poultry in which this pathogen is commonly found. However, even though virtually all types of Salmonella have the potential to cause disease in man, not all are commonly associated with disease in man. Understanding how these processes work is critical to the detection of high risk types of Salmonella in livestock and the food chain, and efforts to decrease the likelihood of Salmonella entering these environments. We propose to study two common types of Salmonella that are both present in pig herds butter present distinct risk to food safety. We will study these bacteria at a genetic and behavioural level to understand how the different types circulate in pig populations in the UK and how they enter and survive in our food. First a collection of pig and food chain isolates of Salmonella Typhimurium will be whole genome sequenced and the variation in their genome used to define the how they spread into the food chain and into the human population. Then we will study important behavioural variations that may impact the threat posed by the variants in food. As the types of Salmonella to be studied are genetically closely related, the number of genetic differences are small, which makes it possible to identify candidate differences associated with altered behaviours of the variants. Genetic differences in types of Salmonella are potential candidates targets for surveillance to identify types more likely to represent a risk to food safety or for other intervention strategies aimed at decreasing the likelihood that they will enter the food chain.

Technical Summary

The considerable economic and health impact of pathogens of the genus Salmonella is the result of their presence in livestock and poultry, entry into and survival within the food chain, and their ability to cause intestinal or systemic disease. However, not all variants of Salmonella are equally likely to cause disease in man and an understanding of the molecular basis of the likelihood that a particular variant will enter the food chain and cause disease in man is critical to food safety. Some variants of Salmonella are prevalent in food animals yet are not a predominant cause of human clinical infections. This research proposal seeks to address these questions using a molecular epidemiology and comparative whole genome sequence approach combined with classical molecular biology and infection models to compare two highly related variants of S. Typhimurium (DT193 and U288) that exhibit distinct risk profiles for foodborne disease in man, despite similar epidemiology in livestock. Little is known about the variation in genotype and phenotype of closely related variants of bacterial pathogens circulating in zoonotic reservoirs and the environment. Crucially, genotypic polymorphisms are not only potential candidate targets for intervention strategies aimed at decreasing the likelihood that these pathogens enter the food chain but also targets for distinguishing variants of pathogens that differ in their risk to food safety, useful for surveillance. This study will define the molecular epidemiology of common variants of Salmonella Typhimurium in the UK pig herds and those entering the food chain via abattoirs by analysis of whole genome sequence variation. Genotypic, transcriptomic and phenotypic variation will be determined and important genotypic differences understood in the context of their associated phenotype by whole genome recombination and mutagenesis approaches.

Planned Impact

Please see documents submitted by lead RO (joint reference Q2094507).

Publications

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Description This joint project with the Institute for Food Research started in November 2015. Our component (lasting 8 months) is scheduled to start in year 3 of the project (2017) and will involve analysis of Salmonella Typhimurium variants in pig ligated intestinal loop and oral challenge models. No findings to report at this stage.
Exploitation Route See above.
Sectors Agriculture, Food and Drink,Pharmaceuticals and Medical Biotechnology