Linking genotype and transcriptome response variation of Salmonella Typhimurium to pathogenicity and survival during transmission from farm to fork

Lead Research Organisation: Quadram Institute Bioscience
Department Name: Contracts

Abstract

Using a diverse collection of field isolates of Salmonella Typhimurium we will identify genotypic features associated with variants that successfully enter the food chain and cause disease in man. Distinct genotypes exhibit different likelihood of entering the food chain and causing disease. For example two genotypic variants commonly isolated from pigs in the last 10 years in the UK, but only one is commonly associated with disease in man. We will address the hypothesis that lineage specific genetic factors impacting survival in the food chain, or the transcriptional response to environmental signals account for the absence of common livestock genotypes entering and causing disease in man. We will determine in representative isolates from across the tree, the diversity of genotype and coding capacity, and transcriptional response to stress factors encountered within the food chain such as low pH, heat, osmotic stress, desiccation and survival / replication in nutrient poor environments. We will investigate the diversity of the S. Typhimurium interaction with the intestinal mucosa. We will address the hypothesis that while some S. Typhimurium variants may enter the food chain they are not a common cause of human disease due to genotype-specific coding capacity or transcriptome response that modulates interactions with the host. We will employ saturating transposon mutagenesis with TraDIS to define essential genes in distinct Typhimurium lineages for survival in the inflamed intestine and survival in stress conditions, an important factor in the transmission of these isolates during infection.
 
Description We have determined the genomic diversity of a representative collection of bacteria of Salmonella Typhimurium and determined their phylogenetic relationship.
We have characterized
• Determine survival in stress conditions of 24 representative isolates of Salmonella Typhimurium
• Determine motility of 24 representative isolates of Salmonella Typhimurium
• Determine biofilm formation of 24 representative isolates of Salmonella Typhimurium
• Determine carbon source metabolic profile of representative isolates of Salmonella Typhimurium and relate to phylogeny

We have identified genome sequence characteristics specific to the most recent epidemic clone of S. Typhimurium and implicated copper homeostasis genes as candidate drivers of the emergence of the most recent clone that accounts for a large proportion of salmonella in humans and animals in the UK currently.

We have completed studies to identify the role of genome sequence that is specific to the epidemic clone that has implications that link current animal husbandry practices to the selection of pathogen bacterial clones.

We have discovered microevolutionary processes mediated by a bacterial virus (phage) that have occurred over very short periods of time during the current epidemic that have the potential to change the transmissibility of the pathogen.
Exploitation Route Our initial findings suggest that the increased use of heavy metals in livestock feed may have contributed to the emergence of the current epidemic clone of Salmonella Typhimurium. We have this hypothesis using in vitro and in vivo infection models to investigate the possible impact of current husbandry policy on the outcome of host colonisation and pathogenicity of bacterial pathogens. This work will lead to information that could be used to inform policy on animal husbandry practices.
Sectors Agriculture, Food and Drink,Environment

 
Description A leading feed company that produces raw dog food is using information on Salmonella contamination in the factory and product to improve their processes and the safety of product Application of expertise developed during this project has been applied to a collaboration with a biotechnology company to develop and bring to market novel antimicrobials.
First Year Of Impact 2018
Sector Agriculture, Food and Drink
Impact Types Societal,Economic

 
Description Molecular epidemiology and genomics of Salmonella Typhimurium in livestock and wild animals 
Organisation Animal and Plant Health Agency
Country United Kingdom 
Sector Public 
PI Contribution My research group designs research programs, processes samples for genome sequencing, analyses data and carries out molecular microbiology studies to test hypotheses generated from sequence analysis. We write manuscripts for publication in peer reviewed journals. We work with our partners to identify potential use of genome sequence data to improve surveillance and diagnostics of foodborne pathogens.
Collaborator Contribution A partners at APHA help to design research programs with advice and epidemiological data from national surveillance programs. They prepare genomic DNA for whole genome sequence and help interpret data and analysis.
Impact Collaboration is multi-disciplinary IFR scientists provide sequence analysis and molecular biology expertise and APHA scientists provide epidemiological expertise
Start Year 2015
 
Description Molecular epidemiology and genomics of Salmonella Typhimurium in livestock and wild animals 
Organisation Public Health England
Country United Kingdom 
Sector Public 
PI Contribution My research group provides expertise in sequencing and analysis of sequence data of foodborne bacterial pathogens and molecular biology for the characterisation of pathogens. My team analyses data and disseminates findings to the scientific community and other groups of interested parties by the preparation of manuscripts or oral presentations. The activity aims to contribute underpinning scientific evidence for bacterial pathogen surveillance and development of intervention strategies aimed at decreasing the likelihood that pathogens will enter the food chain.
Collaborator Contribution Collaborators at PHE contribute surveillance, samples and molecular epidemiology expertise. They contribute to preparation of publication material and monitor potential use of scientific output for translation into surveillance or intervention.
Impact none as yet
Start Year 2015
 
Description AB Agri Ltd introductory meeting to discuss potential areas of collaboration 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Discussion on how work in the Kingsley lab could be used by AB Agri (leading animal feed production company) to increase productivity and food safety in the pig rearing industry.
Year(s) Of Engagement Activity 2017
 
Description Discussions with Mike Salter and Steven Jagger from ABAgri 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Discussions about how work on pathogen variation of Salmonella and transferable copper resistance in the Kingsley lab could be used to increase productivity and food safety in the pig rearing industry.
Year(s) Of Engagement Activity 2016
 
Description Oral presentation and three posters presented at 5th ASM Salmonella Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Dr Rob Kingsley presented a talk 'Genotypic and phenotypic diversity arising during the clonal expansion of the current MDR monophasic Salmonella Typhimurium epidemic', and Dr Priscilla Branchu, Dr Matt Bawn and Dr Mark Kirkwood presented posters entitled 'Altered copper homeostasis in the multidrug resistant monophasic S. Typhimurium epidemic clone'. 'Signatures of microevolution in Salmonella Typhimurium revealed through whole genome sequencing', and 'Molecular Basis of Foodborne Disease Risk of Variants of Salmonella Typhimurium DT193 and U288' to a large group of scientists from around the world with the objective of sharing ideas and research outputs.
Year(s) Of Engagement Activity 2016
URL http://conferences.asm.org/index.php/component/content/article/140-conferences/5th-conference-on-sal...
 
Description Poster presentation at 'Microbes in Norwich' symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact A meeting to exchange ideas and research findings for scientist with an interest in microbes in Norwich. Dr Matt Bawn presentation title 'UK Salmonella Typhimurium Epidemic Associated with Acquisition of Novel Genomic Island'
Year(s) Of Engagement Activity 2017
URL https://www.facebook.com/events/221060494967981/
 
Description Seminar presented at the Roslin Institute, Edinburgh 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited seminar entitled 'Genome variation of Salmonella: epidemics, evolution and pathogenesis'. Dissemination of research findings and plans for several projects. Discussion with research leaders.
Year(s) Of Engagement Activity 2016
 
Description Third year BSc Animal Science students and 2 lecturers from Writtle college visit to Earlham Institute 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Undergraduate students
Results and Impact Dr Matt Bawn met with visiting students from Writtle College and described his work with food borne pathogens including work funded by three BBSRC funded projects. The visit from 19 third year BSc Animal Science students and 2 lecturers from Writtle college in 2016 enabled us to promote our science and highlight colleague career paths in genomics and bioinformatics. It provided a forum for two-way dialogue where staff could engage directly with the students and lecturers, bringing application and relevance to key areas of study. A 'three-horizons' task also prompted the students to consider the potential limitations of current research themes and to consider future possibilities and outcomes. The event also provided Matt with the experience of working with students and the practice of tailoring the communication of their work to varied audiences. 100% of student respondents thought the event was 'great' and would recommend future visits.
Year(s) Of Engagement Activity 2016