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Understanding the dynamics antimicrobial resistance genes flux in the soil, animals and humans in different fertilisation practices in grasslands

Antimicrobials used in human and veterinary medicine end up in the environment where they have important impacts on agricultural and environmental ecosystems and may lead to the emergence of antimicrobial-resistant (AMR) bacteria. Livestock farms may function as reservoirs where genetic material from environmental bacteria transfers to human- or animal-associated bacteria, including zoonotic pathogens. Antimicrobial resistance genes are often associated with mobile genetic elements (MGEs) which capture genetic material from the environment and transfer it between bacterial species. Horizontal gene transfer occurs frequently in the animal gut, but agricultural environments like soils can also function as hotspots for bacterial exchange of genetic material.

It has long been known that the use of low-dose antimicrobial drugs may drive the development of AMR. However, over the last decade, it has been shown that polluted environments with low levels of antimicrobials may contribute to the selection, enrichment, and maintenance of multidrug-resistant bacteria. Such selection pressure could be exerted by

  • Antimicrobial residues from human sewage sludge
  • Using antimicrobials in livestock selecting for antimicrobial-resistant bacteria in the animal’s intestinal microbiome
  • The manure/slurry storage areas and when applied to land as fertiliser

Currently, our understanding of the spread of AMR is limited to small-scale environments, like the animal gut, wastewater treatment plant, manure storage, or soil in a field. Major gaps exist in our understanding of the spread of AMR from “farm to fork.” This includes surveillance and data sharing related to the emergence of AMR in foodborne bacteria and its potential impact on both animal and human health. Therefore, we need to understand and tackle antimicrobial resistance to include integrated studies on AMR bacteria, genes, and mobile genetic elements at the farm level, including livestock and surrounding farm environments. A detailed examination of farming practices in animal production could highlight optimal procedures and how they can be modified to minimise the enrichment and dissemination of antimicrobial resistance.

  • The key challenges driving this research are:
  • Lack of knowledge and understanding of how anti-microbial resistant bacteria and resistance genes flow in a farm environment
  • To improve understanding of the whole ecosystem involved in the spread of AMR using larger- scale studies.
  • To develop best farming practices to tackle AMR, and AMR spread on the farm level
  • Limited data regarding antimicrobial and heavy metal residues in farming systems and the risk of AMR selection and co-selection.
  • Gaining insight into the mechanisms of AMR and understanding short and long-term persistence, and successful transmission. This knowledge is fundamental to the development of novel strategies to tackle AMR.

Food and drink manufacturing: Establishing baseline contributions to climate change and identifying scope for reduction of environmental impacts

Scotland’s food and drink manufacturing sector is an important contributor to the economy, accounting for 31% of the annual turnover of the manufacturing sector. Scotland’s reputation as a land of food and drink is largely driven by the production of high-quality healthy food.

However the positive messaging of Scotland's reputation must be maintained while delivering its ambitious climate change targets. The Scottish Government commits to reducing baseline greenhouse gas (GHG) emissions by 75% by 2030 and transitioning to net zero by 2045. Meeting these targets requires a coordinated approach across all sectors of society including the manufacturing of food and drink.  

Food production generates GHG emissions and agriculture, and related land use, accounted for 24% of the total emissions in 2017, down 29% from the baseline levels of 1990. An update to the Scottish climate change plan has accelerated the drive to net zero and will require transformation across all sectors of society including the food and drink manufacturing sector. This includes transforming the agricultural/food production system and building a greater understanding of the environmental impact of practices associated with the manufacture and distribution of food and drink products.

Enhancing livestock resilience and adaptability to environmental challenge, while protecting and enriching genetic diversity

Scottish agriculture faces significant challenges associated with changing policy, markets, environment, and technology. The agriculture sector needs to maintain and increase profitability by responding to changing market conditions while contributing to Scottish Government commitments on greenhouse gas emissions and biodiversity. The application of genetics is a cost-effective way to improve the productivity and sustainability of livestock, as progress is permanent, sustainable, and cumulative. Genetic improvement is estimated to have resulted in 50-90% of the overall animal improvements over the last 60 years. It is a driver for the improvements in efficiency, productivity, and sustainability of Scotland’s livestock sector. However, despite widespread uptake of genetic improvement in some sectors, such improvements have not been disseminated across the entire Scottish livestock population, particularly in the beef cattle and sheep sectors.

Failing to include genetic diversity and adaptability in selective breeding programmes has serious negative effects on the sustainability of the livestock sector. Maintaining genetic diversity and enhancing farm animal adaptability to the environment are key drivers of long-term sustainability and acceptability of livestock production in Scotland and beyond. Unmonitored directional selective breeding may compromise both diversity and the animal’s capacity to cope with and thrive in an ever-changing environment.

Data driven innovations for improved sustainability of ruminant productions systems

Scotland’s beef, sheep and dairy sectors are under pressure to improve the efficiency of production, health, and welfare, increase financial performance and reduce environmental impact. The dairy-beef sector is fragmented: production of cattle involves a series of supply chain players and limited data sharing occurs along this supply chain, resulting in sub-optimal performance of the sector.

Precision livestock farming (PLF) coupled with data-driven solutions are recognised as important tools in the future of Scotland’s agriculture. When exploited fully, PLF tools can

  • Aid farm-level management
  • Improve animal health, welfare, and productivity
  • Monitor or reduce greenhouse gas emissions
  • Improve traceability of livestock products

Whilst the argument for the adoption of technologies is often clear, the level of uptake has been poor, particularly across beef and sheep sectors. Our previous research and direct engagement with beef, sheep and dairy farmers and supply chain actors identified a lack of accessible information, data and clarity relating to commercially available PLF solutions as a key barrier to uptake. Currently, production and sustainability challenges are addressed by improvements in farm management and investment in isolated PLF solutions, achieving limited progress.

Data solutions which operate across entire supply chains offer enormous potential for improved sustainability. Currently, no system exists to integrate information sources within and between different elements of a supply chain. Recent advances in electronic identification (EID) for cattle (including ultra-high frequency technology), and data integration solutions (e.g., blockchain) can underpin research and development in this area. This is important to drive improvements in product quality and consistency, whilst optimising the efficiency of entire supply chains.

 

Policy brief: "Participatory Research to Identify Inefficiencies and Challenges Across Scottish Ruminant Supply Chains".

Understanding public attitudes and preferences for healthy and sustainable diets

The Food, Agriculture, Biodiversity, Land-Use, and Energy (FABLE) Consortium, a global network of researchers, published a report in 2020 titled “Pathways to Sustainable Land-Use and Food Systems in the United Kingdom by 2050.” This report outlined how sustainable food and land-use systems can contribute to raising climate ambition, aligning climate mitigation and biodiversity protection policies in the UK.  The report recommends that existing and emerging national policies within each of the four UK nations should consider the strong evidence that a healthy diet could play in reducing greenhouse gas emissions and protecting biodiversity. The report also highlights that modelling consumer behaviour is likely to become even more important.

Within Scotland, the “Food Standards Scotland Strategy for 2021-2026: Healthy, Safe, Sustainable: Driving Scotland’s Food Future” incorporates these recommendations in its values and guiding principles. The FSS strategy highlights the role of “social research in understanding what influences human attitudes and behaviour so that policies are capable of driving positive change”.

There are several Goals defined for 2021-2026. One of them consists of delivering a food environment which empowers consumers to make safe, healthy, and sustainable choices. This can be achieved by driving and influencing strategies for improving access to healthy and sustainable diets for the people of Scotland. Another goal is to engage with all parts of society in Scotland, to understand the issues that matter to consumers and provide information that is tailored to their needs. To achieve these goals, we need the best available data and methods to strengthen insights into behaviours, attitudes, and wider food interests of the Scottish population. We also need to integrate evidence from research on public health and demographics to ensure advice on dietary health improvement is targeted to the appropriate population groups for maximum benefit.

Protecting Scotland’s crops: disease resistance and pathogen biology

Scottish agriculture faces significant challenges and opportunities related to changing policy, markets, environment, and technology. More specifically, the agriculture sector needs to maintain and increase profitability by responding to changing market conditions while simultaneously contributing to Scottish Government commitments on greenhouse gas emissions and biodiversity. These objectives must be achieved in an evolving natural environment in which risks, such as increased summer drought, and opportunities, such as increased area of prime agricultural land, are rapidly changing. Underpinning these changes is a need to exploit genetic diversity and accelerate the efficient breeding of crop cultivars adapted to new growing technologies and environments.

The potato and soft fruit industries in Scotland are an economically important part of the agricultural sector. Pathogens and pests, both established and newly emerging, represent major constraints to sustainable crop production. There is a need to develop crops for the future which are more resilient to the changes in climate and require lower high-carbon inputs, such as fertilisers and pesticides. It is important to increase biodiversity by introducing new crops which have increased resilience. Crops with these traits reduce the need for pesticides and thus have a positive environmental impact. Establishing such crops can also extend production seasons, mitigating risk for farmers from sporadic unfavourable growing conditions. Extending the growing season for Scottish soft fruit would also extend the period that fresh locally grown soft fruit would be available for Scottish consumers.

Understanding the diversity of Shiga toxin-producing E. coli and its relationship with human pathogenic potential

Escherichia coli (E. coli) normally occur in the gut of animals, including humans. Most are harmless but some types of E coli cause illness in animals, some in humans, and some in both. Some are harmless to animals that carry them but cause a range of symptoms and clinical signs when they infect humans. These disease-causing E. coli often carry various genes that cause them to produce Shiga toxins. They are referred to as Shiga toxin-producing E. coli (STECs). Different strains of STEC are associated with different degrees of disease in humans, ranging from mild diarrhoea to long-term illness or, in extreme cases, death.

Scotland has more human cases per head of population than any other part of the United Kingdom. We now know a lot about the strains of STEC in Scotland due to the introduction of Whole-Genome Sequencing (WGS). This gives us lots of detailed information about each specific bacterial isolate. WGS is used to look at STEC bacteria isolated from different sources to determine if they are the same, or different. This enables us to tell if they are linked/ For instance, if a human clinical case can be attributed to a specific source, such as another human, animals, the environment, water, or food products. If we can make these links, we can begin to understand how the chain of transmission works. If we understand the chain of transmission, we can target our intervention actions to the point where they are most effective, so breaking the chain. This way we can reduce the burden of disease in the Scottish human population, reduce health service costs and save lives.

Novel vaccines to combat significant endemic diseases of livestock in Scotland: Gastrointestinal nematode parasites of ruminants

Sustainability and food security are two key challenges for the UK agricultural sector. In a changing climate, there is a need to reduce the impact of endemic diseases on livestock health, welfare, and productivity. The brown stomach worm, Teladorsagia circumcincta, is the most prevalent livestock roundworm parasite in the UK and has a major economic impact on the sheep industry. This is due to production losses attributed to reduced live-weight gain and costs associated with treating the problem. The losses cost around £84 million every year (2005 figures). This is equivalent to £4.40 extra per lamb to achieve finishing weight. For the same reasons, the nematode species Ostertagia ostertagi, poses a problem in cattle production.

Current roundworm control relies heavily upon a handful of broad-spectrum compounds (anthelmintics). Unfortunately, roundworms are developing resistance to these to these treatments which allow them to survive. 

Other key drivers for this research are:

  • The limitations of the current chemotherapeutics
  • Reduced efficacy and anthelmintic resistance
  • The effects of residues on the environment, operator and food safety

The development of synthetic vaccines might help in mitigating the effects of nematode infection that could be used in conjunction with athelmintics. The initial step for vaccine development is the procurement of host antibodies, produced by either exposing sheep to continuous infection with the sheep-parasitic nematodes, or by vaccination of cattle with complex protein mixtures that induce protection against cattle-parasitic nematodes. These antibodies are then used as the basis for the identification of individual proteins from the nematodes, which can then be incorporated in the vaccines.

Novel vaccines to combat significant endemic diseases of livestock in Scotland: Vaccines for reproductive diseases

Reproductive pathogens in sheep

Chlamydia abortus, the bacterial pathogen is responsible for the death of lambs and the cause of a disease known as enzootic abortion of ewes. This is the most common infectious casue of lamb death in Scotland, that is also zoonotic (i.e., can result in infections of humans) and can result in spontaneous abortion and stillbirths in humans, and death of the pregnant mother. Over the last 60 years, several inactivated vaccines have come and gone due to high production costs, manufacturing difficulties, low efficacy, and disease outbreaks.

Our previous work has shown that live vaccines can cause disease in some animals, while recent evidence shows the live vaccine strain is not attenuated. There is a clear need to produce a better vaccine, which will provide increased stability, reduce shedding of infectious organisms at parturition and be more economical to manufacture. Additional research has revealed the main targets for developing a recombinant subunit vaccine, as well as for the delivery of antigens using viral vectors.

 

Reproductive pathogens in Cattle

Neospora caninum is a parasite that can result in abortions in cows, sheep and goats and is the most diagnosed infectious cause of abortion in cattle in Scotland while it also been confirmed as a cause of abortions in sheep and neonatal mortality in lambs in the UK and worldwide. There are no vaccines that prevent abortions caused by Neospora or that prevent transmission from dam to foetus in uterus.

Novel vaccines to combat significant endemic diseases of livestock in Scotland: Vaccine Delivery Platforms

Infestation of the skin with Psoroptes Ovis (sheep scab mite) represents a major animal welfare and economic burden on the sheep industry. A prototype sheep scab vaccine is effective at controlling sheep scab with an efficacy of over 80% (lesion size reduction). However, the development of a vaccine was considered a ‘market failure.’ The ever-decreasing amount of treatment options means sustainable control approaches are becoming more attractive.

Bovine Respiratory Disease (BRD) in cattle remains a significant problem in the beef and dairy industries. BRD is caused by a variety of infectious agents. Most outbreaks start with viral infection. The key viruses involved in the disease are respiratory syncytial virus (BRSV), parainfluenza 3 virus (PI3V), bovine herpesvirus 1 (BHV-1) and bovine viral diarrhoea virus (BVDV). BRD is still a significant problem despite several vaccines and medications being commercially available. This suggests these options are not sufficiently effective.

BVDV eradication in Scotland has progressed well and is no longer an issue. Vaccines for the other viruses are moderately protective against disease but ineffective in controlling the spread of disease. Modified live vaccines induce broader, more complete immune responses. However, viral proteins have evolved to significantly interfere with the immune response. Further, modified live virus vaccine strains of BHV-1 can appear in vaccinated animals and, when reactivated reduce the immune response. Similar latency and reversion issues appear for virulence bovine respiratory syncytial virus.

In sum, there are several key challenges related to:

  • Overcoming the limitations of the current chemotherapeutics; reduced efficacy and antibiotic resistance; and the effects of residues on the environment, operator, and food safety.
  • Providing increased productivity and efficiency in livestock production with the economic, food security and environmental benefits which accrue from that.

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  • Biomathematics and Statistics Scotland
  • The James Hutton Institute
  • The Moredun Group
  • The Rowett Institute
  • The Royal Botanic Garden Edinburgh
  • Scotland's Rural College (SRUC)
The Scottish Government 

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