Incorporation of whole ecosystem approaches to reduce transmission of foodborne pathogens and antimicrobial resistance
Project Lead
Challenges
Farm animals are a major source of key zoonotic pathogens of humans, including those causing enteric disease like Campylobacter spp., Salmonella spp., enterotoxigenic Escherichia coli and Clostridioides difficile. There are around 2.4 million cases of foodborne pathogen infections annually in Scotland, with a financial burden of £9 billion. Reducing the carriage of zoonotic pathogens within the gastrointestinal tract of farm animals has clear potential to reduce the incidence of human foodborne disease. Importantly, many bacteria (both pathogenic and those commensal bacteria inhabiting the gastrointestinal tract) carry antimicrobial resistance genes, often located on mobile DNA. The transfer of AMR genes between unrelated bacteria contributes both to the environmental spread of AMR and to the evolution of multidrug resistance (MDR) pathogens.
Given the rise of MDR pathogens, and the need to reduce antimicrobial use, alternative approaches are required to reduce pathogen carriage in animals, and subsequent transmission to humans. One of the most potent defences animals have against invading pathogens is their indigenous microbiome. This dense community of beneficial microbes provides a robust defence against incoming pathogens by outcompeting or killing them, thereby reducing their colonisation, disease-causing activity, and onward transmission. This has led to increasing interest in developing gut bacteria as “Live Biotherapeutics” and their associated bioactive products, as alternatives to antibiotics.
In short, it is paramount to further understand the role of zoonotic pathogens in the dual crises of foodborne pathogens and antibiotic resistance and to identify novel avenues for interventions to reduce the incidence of foodborne disease derived from pathogens and AMR transmission from the environment.
Questions
- What are the sources and epidemiology of foodborne disease in Scotland and what interventions can be introduced to reduce foodborne disease and the associated spread of AMR?
Solutions
This project aims to develop novel approaches to break the chain of transmission of foodborne pathogens and antimicrobial resistance from farm to fork, across a range of environmental ecosystems. The project can be divided into two parts:
Identifying microbes with the ability to inhibit the growth of a range of key zoonotic and foodborne pathogens
We aim to identify microbes that can inhibit the growth of important zoonotic and foodborne pathogens. Key ecosystems, such as the chicken gut and soil, are utilised in the search for such bacterial strains. Characterisation of these strains includes screening for the ability to inhibit the growth of multi-drug resistant pathogens, and could therefore open opportunities to develop alternatives to antimicrobials in the elimination of zoonotic pathogens, with the added benefit of reducing the AMR gene pool.
Understanding the role of zoonotic bacteria in the spread of AMR from farm to fork
We are also improving our understanding of the role of zoonotic bacteria in the spread of AMR through the environment from farm to fork, and the impact this has on the AMR gene pool in the resident gastrointestinal microbiome and clinically important pathogens. For this, we are using our existing Campylobacter whole genome sequence resource to determine linkages between the carriage of multiple AMR genes, heavy metal resistance (HMR) genes and mobile genetic elements. We will then compare the presence of specific genes identified with the incidence of similar genes within the commensal microbiota of farm animals and humans. This research is increasing our knowledge of the impact of co-selective factors, such as heavy metals and biocides, in promoting the persistence and spread of AMR.
The key deliverables for this project are:
- Isolating novel bacterial strains from chickens and environmental samples to identify strains with antimicrobial activity against important zoonotic and food-borne pathogens
- Determining genetic linkages between the carriage of multiple antimicrobial and heavy metal resistance genes and mobile DNA.
- Establish the impact of co-selective factors in AMR transmission.
- Establish the prevalence of identical genes in zoonotic pathogens and the commensal gut microbiota in diverse hosts.
Project Partners
Progress
In the first year we initiated work on both parts of the project.
Identifying antibacterial activity of commensal bacteria towards zoonotic pathogens: Through collaboration with other SEFARI researchers, we have identified sources for the required samples and established methods to culture novel bacterial strains from soil and chicken gut samples. We isolated more than 100 individual bacterial strains from the chicken samples, that represent 25 different bacterial genera, with 16 potentially novel species as determined based on phylogenetic analysis. Selected strains from this collection, will go on to be screened to identify those with antibacterial potential.
We have also started screening commensal strains within the Microbiology group's extensive culture collection to assess antibacterial activity. We initially focussed on the pathogens Escherichia coli, Salmonella enterica and Clostridioides difficile. Twenty bovine isolates were screened revealing specific isolates with activities against each of these three pathogens. These isolates will now be checked to determine any activities against additional foodborne pathogens (including multi-drug resistant strains).
Establishing the role of zoonotic bacteria in AMR transmission from farm to fork
From our database of almost 7000 Campylobacter whole genome sequences, we have identified those genomes that contain genes providing resistance to the heavy metals copper, zinc and mercury. Although the gene responsible for resistance to the antibiotic tetracycline was found in the same genomes that also have copper resistance genes, these genes did not occur on the same mobile genetic element. This data has been added into the emerging metadata spreadsheet for Campylobacter spp. In future work, the resistance phenotype of these strains will be confirmed and the potential for gene transfer established.
Knowledge exchange:
A leaflet showcasing the work on Antimicrobial Resistance was developed in partnership with other SEFARI scientists and distributed at the Royal Highland Show (June 2023).
A one page science/policy brief was prepared together with other SEFARI researchers summarising Strategic Research Programme work on AMR in the environment and submitted to the Rural and Environment Science and Analytical Services Division (RESAS) of the Scottish Government for distribution to external stakeholders (October 2023).
A poster on tetracycline resistance in Campylobacter species entitled: “Sequence and structure comparisons of tetracycline resistance proteins: impact of resistance phenotype” was presented at the International Gut Microbiology conference in Aberdeen (June 2023). This conference was organised by Rowett Institute PIs and included a session on the use of the microbiome to reduce infectious disease in animals.
A Podcast entitled ‘The Pros and Cons of Antibiotics’ was released during Antibiotic Awareness week (Nov 2022).
A podcast focussed on the role of the gut microbiome on health (for animals and humans) was recorded as part of the Inside Matters* series. Weblink: https://insidematters.health/episodes/episode-021-professor-karen-scott
During the second year, we continued work on both parts of the project.
Identifying antibacterial activity of commensal microbes towards zoonotic pathogens:
We have completed the work isolating bacterial strains from different samples, building a collection of more than 400 strains of soil bacteria representing at least 90 distinct species and a further 30 distinct genera isolated from chicken samples. Representative strains for each species have been tested for activity against important livestock pathogens (Salmonella enterica, Escherichia coli, Clostridioides difficile and Campylobacter jejuni), using two assays. We have identified individual isolates able to inhibit growth of against at least one of these pathogens. We generated whole genome sequence data for the most important isolates and will use these to investigate the mechanistic basis for the previously observed inhibitory activity against pathogens.
Establishing the role of zoonotic bacteria in AMR transmission:
Campylobacter isolates harbouring multiple antimicrobial and/or heavy metal resistance genes were identified from genome sequence data. A subset of fourteen multi-resistant and one sensitive Campylobacter strains were tested for their ability to grow in the presence of different concentrations of antibiotics and heavy metals. One isolate was resistant to all four antibiotics and highly tolerant to cobalt, iron and zinc. Another isolate, tolerant of all heavy metals was highly resistant to ampicillin and tetracycline. Finally, the sensitive isolate grew poorly in the presence of all the heavy metals and antibiotics. The results showed some there may be some correlation between the presence of antibiotic and heavy metal resistance. A prototype searchable database including phenotypic, genotypic and metadata has been assembled and trialled. Resistance genes identified in this work will be compared to those found in linked SEFARI projects, determining the incidence of identical resistance genes on commensal and pathogenic bacteria, building our knowledge about the environmental flow of AMR.
Knowledge exchange and other outputs
- The three PIs co-organised the 13th biennial International Gut Microbiology Symposium (13-15th June 2023) which included a scientific session on “One Health” and another on “Interactions between microbiota, pathogens and host”. During this conference, a poster was presented on the Campylobacter AMR studies.
- AW gave a talk at a RANK Forum workshop in June 2023, discussing the impact of food security inequalities on health, with a focus on impacts mediated by the gut microbiome.
- AW was a participant at a meeting at the House of Lords in November 2023, aimed at improving the visibility of UK microbiome research.
- KS led the arguments ‘against’ in a debate on the Pros/Cons of Microbiome profiling, at the Beneficial Microbes conference in Amsterdam, Nov 2023.
- AW was a speaker and session chair at a microbiome safety workshop in London, organised in January 2024 by the Microbiology Society, to assess the potential safety concerns around microbiome-targeted interventions.
- SD participated in a discussion group meeting with Scottish farmers, food producers and an Aberdeenshire councillor (Industry support executive) on One Health and the environment
- SD wrote an article for The Conversation on one of our gut microbiota species with inhibitory activity against multiple pathogens – Gut microbiome meet Ruminococcus bromii the microbe that loves carbs.
Podcasts
- Alan Walker was a guest on the "Inside Matters" podcast series, talking about gut health and microbiomes.
- Karen Scott was a guest on the "Inside Matters" podcast series, talking about probiotics, antimicrobials and gut microbiomes.
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