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: UNLISTED
Abstract
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Technical Summary
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.
Planned Impact
unavailable
People |
ORCID iD |
| Robert Kingsley (Principal Investigator) |
Publications
Feasey NA
(2014)
Drug resistance in Salmonella enterica ser. Typhimurium bloodstream infection, Malawi.
in Emerging infectious diseases
Kariuki S
(2015)
Ceftriaxone-resistant Salmonella enterica serotype typhimurium sequence type 313 from Kenyan patients is associated with the blaCTX-M-15 gene on a novel IncHI2 plasmid.
in Antimicrobial agents and chemotherapy
Klemm EJ
(2016)
Emergence of host-adapted Salmonella Enteritidis through rapid evolution in an immunocompromised host.
in Nature microbiology
Métris A
(2017)
SalmoNet, an integrated network of ten Salmonella enterica strains reveals common and distinct pathways to host adaptation.
in NPJ systems biology and applications
Okoro CK
(2015)
Correction: Signatures of Adaptation in Human Invasive Salmonella Typhimurium ST313 Populations from Sub-Saharan Africa.
in PLoS neglected tropical diseases
Okoro CK
(2015)
Signatures of adaptation in human invasive Salmonella Typhimurium ST313 populations from sub-Saharan Africa.
in PLoS neglected tropical diseases
Ondari EM
(2017)
Role of sapA and yfgA in Susceptibility to Antibody-Mediated Complement-Dependent Killing and Virulence of Salmonella enterica Serovar Typhimurium.
in Infection and immunity
| 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. Expertise and knowledge of variation in epidemiology and function of Salmonella pathovariants has been used to influence WHO and IVI to develop a Full Value of Vaccines Assessment (FVVA) for vaccines against invasive non-typhoidal Salmonella (iNTS) disease |
| First Year Of Impact | 2018 |
| Sector | Agriculture, Food and Drink,Healthcare,Manufacturing, including Industrial Biotechology |
| Impact Types | Societal Economic Policy & public services |
| Description | Invited member of the PATH-SAFE Consortium Data Platform Development Effort Community Input Advisory Group |
| Geographic Reach | Europe |
| Policy Influence Type | Participation in a guidance/advisory committee |
| URL | https://www.food.gov.uk/our-work/path-safe-programme-national-foodborne-disease-genomic-data-platfor... |
| Description | BBSRC ICURe Explore Programme |
| Amount | £35,000 (GBP) |
| Organisation | United Kingdom Research and Innovation |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2024 |
| End | 06/2024 |
| Description | Copper-induced microbiota shifts and its effect on pig-gut colonisation by sil and sopE encoding Salmonella |
| Amount | £490,482 (GBP) |
| Funding ID | BB/W003155/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2022 |
| End | 12/2025 |
| 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 | Nestle - Molecular basis for variation in physiological resistance of Salmonella enterica during minimal heating of chilled plant protein foods |
| Organisation | Nestlé (Global) |
| Country | Switzerland |
| Sector | Private |
| PI Contribution | The outcome of this objective will be a comprehensive understanding of the phylogenetic relationship and genome sequence variation of candidate Salmonella strains with increased thermal tolerance and other Salmonella strains not implicated in outbreaks from processed foods. 10-20 representative strains will be selected and their thermal inactivation dynamics will be determined. Whole genome functional screens using saturating transposon mutagenesis and transposon insertion site sequencing (TraDIS) will be used to identify conditional-essential genes required for maximum tolerance to heat and organic acid inactivation. |
| Collaborator Contribution | Insight into industrial processes and relevance to food safety. Advice on impact of research on the food industry. |
| Impact | In progress |
| Start Year | 2018 |
| 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 | Cardiff School of Medicine Science Seminar series |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | Invited keynote seminar at the University of Cardiff School of Medicine presentation entitled 'Salmonella Variants of Interest and Concern: carving a Niche in the pork industry'. Dissemination of key findings from a number of project from within my research group to an audience of approximately 50 students, postdoctoral scientists and prinicpal investigators. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Contributor to The Biofilm Brainhub website |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Website highlighting the role of biofilms in Industry, farming and food. Aimed at the non-specialist. Recent research from my research groups on Biofilm formation by Salmonella was highlighted and a link to the primary literature provided. It is expected that this resource will increase public awareness of biofilms and the risk they play in agriculture. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://biofilmbrainhub.co.uk/ |
| Description | Discussion with Cranswick Foods directors |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | Full day discussion session to share information and develop collaborations on food safety |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://cranswick.plc.uk/ |
| Description | Discussion with a leading producer of raw pet food |
| 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 with a leading producer of raw pet food to implement phage antimicrobials to improve the safety of product. |
| Year(s) Of Engagement Activity | 2024 |
| Description | Discussion with representative from the British Retail Consortium |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Discussion with representative from the British Retail Consortium to identify potential implementation of phage antimicrobials to combat bacterial pathogens in the food chain |
| Year(s) Of Engagement Activity | 2024 |
| 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 | Expert consultation on non-typhoidal Salmonella (NTS) and broadly protective Salmonella vaccines (NTS, paratyphoid A, typhoid) |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Third sector organisations |
| Results and Impact | WHO convened this 2-day expert consultation as a forum for stakeholders to review the evidence on the epidemiology and the serovar distribution of invasive and diarrheal NTS disease, and to discuss how the geographic diversity of Salmonella serovars and the potential demand of endemic countries should be considered in the development of broadly protective Salmonella vaccines. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Expert consultations on invasive non-typhoidal Salmonella (iNTS) vaccines invited participant |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Third sector organisations |
| Results and Impact | Under a recently awarded 3-year grant by the Wellcome Trust, IVI, WHO and other global partners are collaborating to develop a Full Value of Vaccines Assessment to understand both the general and specific value of investment in an iNTS vaccine (or vaccines) and potential to combine with a Typhoid / paratyphoid vaccine. The long-term goal of this FVVA project is to pave the way for the development of safe and efficacious iNTS vaccines, licensure, policy recommendations from SAGE, WHO prequalification, Gavi financing, UNICEF purchasing and national technical advisory group recommendations for use. |
| Year(s) Of Engagement Activity | 2021 |
| 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 | The NIHR Health Protection Research Unit in Genomics and Enabling Data Conference 2024 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | The NIHR Health Protection Research Unit in Genomics and Enabling Data Conference 2024 |
| Year(s) Of Engagement Activity | 2024 |
| 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 |
| Description | Wellcome/BMGF NTS CHIM Workshop invited speaker |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Third sector organisations |
| Results and Impact | Nontyphoidal Salmonellae, particularly Salmonella enterica serovars Typhimurium and Enteritidis, are a major cause of enterocolitis globally. In sub-Saharan Africa NTS are also responsible for invasive disease known as invasive NTS disease or iNTS disease: bacteraemia and/or meningitis which particularly affect young children and HIV-infected individuals and have high associated case fatality rates (1,2). Effective treatment of iNTS disease is hampered by the lack of a pathognomonic clinical presentation, need for blood culturing to make a diagnosis and increasing levels of antimicrobial resistance. For these reasons, development of a vaccine against iNTS disease could have a major global public health impact. New candidate vaccines against iNTS disease have recently entered or are about to enter first-in-human trials, alone or in combination with licensed typhoid conjugate vaccine, making this workshop particularly timely. A controlled human infection model (CHIM) could have a role in the pathway to vaccine registration for healthy and special populations, Objectives of the Meeting 1. Understand possible roles for an NTS CHIM 2. Gauge utility of an NTS CHIM for vaccine development 3. Discuss different approaches to NTS CHIM development 4. Prime Wellcome's call for Expressions of Interest for NTS CHIM development |
| Year(s) Of Engagement Activity | 2021 |