Whole-genome functional analysis of the host-adapted Salmonella Typhimurium DT8

Lead Research Organisation: Quadram Institute Bioscience
Department Name: Contracts

Abstract

The substantial economic and health impact of pathogens of the genus Salmonella is the result of their entry into and survival within the food chain, and their ability to cause disease. Salmonella are a diverse group of pathogens in which some variants are more likely to be associated with disease in humans than others. One of the factors governing this is the adaptation to host species that are important sources of food. Recently an epidemic spanning three years was associated with S. Typhimurium (STM) DT8 that was specifically associated with duck eggs. Recent research from my lab revealed that DT8 is part of a cluster of genotypes adapted to circulation in populations of poultry, ducks and geese. But what are the genomic or transcriptomic features specific to these clusters that result in their association with the avian host and transmission through the food chain? Polymorphisms associated with essential genes, or altered transcriptional response of essential genes, that are specific to strains belonging to genotypic clusters associated with altered risk to food safety are candidate molecular markers of risk to food safety. The overall aim of this project is to determine the essential genes and transcriptional response of STM DT8 compared with non-DT8 variants. The central hypothesis is that a distinct transcriptional response and sets of genes are associated with S. Typhimurium DT8 in environments encountered in the host and during transmission. The significance of the project is that it will inform strategies to intervene in transmission of food borne pathogens through the food chain and identify pathogens in their zoonotic reservoirs.

Publications

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Description The relationship of Salmonella Typhimurium DT8 isolates compared with other Salmonella Typhimurium was determined by analysis of whole genome sequence. Additional and distinct epidemics of DT8 Salmonella disease in ducks was detected that was not previously known. Strains that were representative of the the epidemics were selected for phenotypic analysis. Multicellular behaviour in biofilms and ability to invade animals cells in culture was determined and compared with diverse variants of Salmonella. Analysis of transcriptional response to elevated temperature was initiated. DT8 transcriptional responses to elevated temperatures has been determined.

We carried out a retrospective analysis of approximately 280 S. Typhimurium strains isolated from ducks in the last 20 years in conjunction with more recent human isolates to investigate the epidemiology of Salmonella in ducks. S. Typhimurium strains DT8 and DT30 originating from other animal species were also included in the panel in order to provide further insight into the 2010 epidemic affecting human health. We also addressed the questions of whether the DT8/30 isolates in the UK were part of a single epidemic clonal complex and how they are related to previously circulating DT8/DT30 and S. Typhimurium phage types.

• Most S. Typhimurium DT8 and DT30 strains were present in a distinct but relatively diverse phylogenetic clade.
• DT8 were the majority and ancestral type, with occasional independent emergence of DT30 from DT8 ancestors.
• Most DT8 and DT30 strains were isolated from ducks and occasionally also wild avian species, rarely from livestock species. Suggesting that the genotype was adapted to circulation in duck and related avian host species.
• Isolates from the period of an outbreak in the human population between 2009 and 2011 were from two distinct clades (A and B) with the majority from clade B.
• Clade B was itself present as two subclades (B1 and B2), with a topology consistent with two independent transmission chains that occurred concurrently in UK duck populations.
• Closely related strains to those in the epidemic clades B1 and B2 were isolated approximately a decade before the outbreak consistent with the presence of the strain in the UK duck population prior to the duck egg-associated outbreak in the human population.
• The strains that were deeply rooted and basal to the main UK epidemic clade were isolated in France, suggesting that there may be a link of the spread of this subclade with French duck farms. It si not clear the direction of spread between these geographical locations before the epidemic spread.
• The most deeply rooted and basal strains from clade B2 that were isolated before the outbreak in people were from the UK, suggesting that the spread of this subclade likely originated in the UK. Isolates from Ireland and Italy were interspersed with those from the UK in both epidemic sub-clades suggesting spread between these locations.

DT8 strains had a unique transcriptional response to culture at elevated temperature, mimicking the conditions in the avian host. This is consistent to a transcriptional adaptation to the avian host.
Exploitation Route A manuscript describing some of our findings is in preparation and data is additionally being used as preliminary data for uplift funding funding. We have discussed our findings with collaborators at the Animal and Plant Health Agency and we are currently preparing a report that will be used to inform surveillance of the duck rearing industry in the UK.
Sectors Agriculture, Food and Drink,Healthcare,Government, Democracy and Justice

 
Description We have ,et with colleagues at APHA and PHE to discuss our findings. We are currently drafting a report that will influence the surveillance of Salmonella on duck farms.
First Year Of Impact 2018
Sector Agriculture, Food and Drink,Healthcare
 
Description EFSA Scientific Colloquium 24 -'omics in risk assessment: state of the art and next steps
Geographic Reach Europe 
Policy Influence Type Participation in a advisory committee
URL https://www.efsa.europa.eu/en/supporting/pub/en-1512