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

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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

10 25 50
 
Description This joint project with the Quadram Institute (formerly the Institute for Food Research) started in November 2015. Our component lasted approximately 8 months and commenced in the autumn of 2018, with a no-cost extension agreed to June 2019. It involved analysis of the virulence of Salmonella Typhimurium variants in pig models. Three strains of S. Typhimurium DT193 and three strains of variant U288 were tested by oral inoculation of four pigs using a novel sequencing-based approach to define the abundance of each strain before and after infection with a pool of all six strains (Vohra et al. 2018. Appl. Environ. Microbiol 84(4):e02262-17). Sequence-based analysis of these pools indicated that U288 strains were slightly more invasive in pigs, albeit statistical significance was not reached. One strain each of DT193 and U288 was selected from this analysis for inoculation of pigs with single strains. This broadly supported phenotypes observed by sequence-based analysis, and revealed that the DT193 strain caused more severe diarrhoea. Findings have been accepted for publication in Communications Biology linked to genome sequence data and other phenotypes for the strains used. A DOI was not available at the time of submission. Co-investigators Stevens and Kingsley have been invited to contribute a review article on Salmonella pathogenesis and host-adaptation in farmed animals for Current Opinion in Microbiology and an advanced draft has been prepared.
Exploitation Route The project may identify markers of the differential virulence or zoonotic risk of Salmonella isolates. In turn this will help to focus research on those pathovariants that pose the greatest risk.
Sectors Agriculture, Food and Drink,Pharmaceuticals and Medical Biotechnology

 
Description Collaboration with the Quadram Institute 
Organisation Quadram Institute Bioscience
Country United Kingdom 
Sector Academic/University 
PI Contribution This is a joint project with the Quadram Institute, where the lead Principal Investigator is Dr Rob Kingsley. The BBSRC contribution to our component of the project is £123,594. It is envisaged that we will evaluate the virulence of variants of Salmonella enterica serovar Typhimurium in porcine models, both to quantify the magnitude and duration of intestinal colonisation in orally challenged pigs and the ability of strains to induce secretory and inflammatory responses in a porcine surgical model.
Collaborator Contribution The Quadram Institute will select Salmonella strains for testing in vivo, based on analysis of their genome sequences, transcriptomes and the phenotypes of the strains in cell-based assays.
Impact None at this stage. We await strains for testing.
Start Year 2015
 
Description Public lecture entitled Confronting the Microbial Menace in Our Food'. Professor Mark Stevens 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact The inaugural lecture of Professor Mark Stevens was held on 30 October 2017 on his BBSRC-funded research to identify bacterial and host factors influencing the ability of Salmonella, Campylobacter and E. coli to colonise farm animals and cause disease. It was attended by children from local schools, members of the public, students at The Roslin Institute and wider University of Edinburgh and posted online.
Year(s) Of Engagement Activity 2017,2018
URL https://media.ed.ac.uk/media/Inaugural+lectureA+Confronting+the+microbial+menace+in+our+food/1_x5k5e...