Salmonella Pathogenesis and Control

Background

Salmonella is a harmful bacterium of global importance. It can cause severe infections in farmed animals and passes through the food chain and farm environment to humans where it causes diarrhoeal illness. Salmonella is estimated to infect over 78 million people each year, resulting in 59,000 deaths. Although vaccines and biosecurity measures have been partly successful in reducing contamination of poultry meat and eggs a pressing need exists to combat Salmonella in livestock, where it can cause diarrhoea, abortion and typhoid-like disease.

Research

Work by the team of Professor Mark Stevens at The Roslin Institute has provided valuable insights into how Salmonella colonises the intestines of farm animals and produces disease. This has involved the use of novel sequencing-based approaches to determine the function of thousands of Salmonella genes during infection with minimal use of animals¹ and to assess the risk of different strains². His team also uses surgical models to study how Salmonella causes gastroenteritis and escapes the gut to cause disease in other parts of the body³.

Impact

The Stevens laboratory has collaborated with industrial partners to apply knowledge gained via research, including by testing vaccines and analysing the basis of host resistance toward selective breeding. The surgical models and genetic approaches used by the team greatly reduce the number animals needed to study bacterial pathogenesis. This was recognised by an international prize for research that has advanced the 3Rs  in the development of veterinary medicines (i.e. the reduction, refinement & replacement of animals in research). Expertise & Models

The LARIF has facilities to inoculate cattle, pigs and chickens with Salmonella, as well as other Hazard Category 2 pathogens, including those that have been genetically modified. Recent examples of collaborative research include analysis of the genetic basis of fowl typhoid resistance with Hy-Line and research on host and bacterial factors influencing bovine salmonellosis with Zoetis. Professor Stevens is part of a consortium led by the London School of Hygiene and Tropical Medicine thatsecured £5.7 million from the BBSRC to develop vaccines against avian and zoonotic pathogens. His work in poultry is greatly aided by resources and expertise provided by the National Avian Research Facility at Easter Bush, including unique chicken lines, immunological tools and capacity for genome modification.

Key Publications:

1. Chaudhuri RR et al. 2013. Comprehensive assignment of roles for Salmonella Typhimurium genes in intestinal colonization of food-producing animals. PLoS Genet 9:e1003456.

2. Vohra P et al. 2017. Quantifying the survival of multiple Salmonella enterica serovars in vivo using massively-parallel whole genome sequencing to predict zoonotic risk. Appl Environ Microbiol 84:e02262-17.

3. Pullinger GD et al. 2007. Systemic translocation of Salmonella enterica serovar Dublin in cattle occurs predominantly via efferent lymphatics in a cell-free niche and requires type III secretion system 1 (T3SS-1) but not T3SS-2. Infect Immun 75:5191-9.