Antimicrobial resistance: bringing Scottish expertise together to find the solutions

Antimicrobial resistance (AMR) is a global, immediate and ongoing concern to human health. AMR occurs when microbes become resistant to clinical or veterinary drugs that are used to treat disease, and this has major consequences on how microbial diseases are managed and therefore how antimicrobial compounds are used.

AMR and antimicrobial usage (AMU) affects different aspects of our lives and environment, and this is reflected in ongoing research. Examples of the breadth of our work includes research on estimating the levels of resistance in sheep, surveillance of AMR genes in Scottish soils and understanding how resistance occurs in priority foodborne pathogens.

Stage

Work in Progress

Directory of Expertise

Purpose

Antimicrobial resistance (AMR) is one of the most important health challenges in the modern era, recognised internationally by the World Health Organisation (WHO) global action plan. The early success of antibiotics in disease control led to unprecedent improvements in human and veterinary healthcare. However, decades later, we are faced with the consequences of their universal and over-use, and the associated development of microbial resistance to antibiotics (and other antimicrobials). We know that AMR can be generated in agriculture by over-use of drugs, resulting in the emergence of resistant bacteria that can then be transferred to humans directly, via food or via the environment. Consequently, it is important to future human health to understand the occurrence of and selection for antimicrobial resistance in agriculture, and the transmission of resistant organisms to humans, putting AMR firmly into the ‘One Health’ agenda.

Across SEFARI our work includes research on antimicrobial and antibiotic resistance within rural agriculture and environmental settings. The work covers a wide range of topics from antimicrobial usage to the surveillance of microbes and development of resistance, and spans a range of agricultural environments to better understand the sources, reservoirs and transfers of antimicrobial genetic determinants, including farmed animals, wildlife, retail food, soil and water.

To help reduce the risk of evolution and transfer of antimicrobial resistance it is also vital we discuss our findings with key stakeholders, such as the Scottish Government and Food Standards Scotland. Consequently, in February 2020, SEFARI scientists organised a joint meeting to discuss AMR research and define the scope of research which is still needed. The event extends a previous open event on AMR hosted by SEFARI scientists. A key aim of the meeting (held February 2020), was to collate and coordinate our research and establish how findings fit within the wider context. By bringing together researchers and stakeholders from a range of different disciplines we sought to define the scope of the work (completed, on-going and still needed), identify synergies, and map onto established networks to enhance our efforts and impact. The meeting illustrated the strengths of our work in a wider, nationally relevant scale.

Results

Key areas of work were identified and grouped into areas relevant to Scottish agriculture. These were then mapped onto established networks of antimicrobial transmission, (such as the one adopted by the Department of Health) to generate an ‘AMR systems map’ for Scottish AMR research.

The map illustrates the scope of our work and shows that most of the known transmission pathways are being researched, to at least some extent within SEFARI, with a focus on resistance in farmed animals, and in environmental habitats. The full map, complete with Strategic Research Programme (SRP) details (e.g. Research Deliverable (RD), Objective (O) and university partner numbers) and hyperlinks to further information can be accessed here.

Our four main research areas identified are in:

Livestock Production,
Transfer of AMR via Food,
Responses to Infection and
AMR in the Environment.

Some examples of our work are:

Determining the level of AMR resistance in farmed animals is not straightforward because there are different ways to measure resistance levels. We found that AMR in sheep can be assessed either from individual bacteria isolated from a sheep faecal sample, or from the complex mixture of all bacteria within the sheep faecal sample, but the choice of method influences the apparent prevalence of AMR. Therefore, a new mathematical modelling method was developed to readily estimate the proportion of resistant bacteria. The information gained from the new method shows where the variation in AMR exists, e.g. between animals or farms. In turn this helps to determine how sampling can be carried out efficiently and also identifies likely predictors of resistance.

Surveillance of AMR genes in environmental habitats has resulted in the production of a Scottish nationwide map of hundreds resistance gene abundances in rural soils. The data shows that while some forms of resistance are an endemic part of microbial ecology in soils, others are localised, and the genetic diversity is driven by environmental factors (e.g. heavy metals) and agricultural practices.

Camplyobacter jejuni is a food-borne pathogen associated with poultry, and responsible for the greatest number of bacterial foodborne disease incidents in Scotland. Development of resistance to clinical antibiotics in foodborne pathogens like Camplyobacter rely on conventional methods for detection that are often time consuming and labour intensive. To aid diagnostics, a rapid surveillance tool is under development for pathogens resistant or susceptible to antibiotics (e.g. E. coli) that generate unique ‘fingerprints’. It is a developing technique with the key advantage that it shortens turnaround time by 2-3 days to pathogen identification.

The process of how resistance is generated to one antibiotic (tetracycline) has uncovered multiple mechanisms of action for the bacteria Camplyobacter jejuni. Most bacteria isolated from infected patients have a low level of intrinsic resistance, which acts by pumping the drug out of the bacterial cells. In addition, some encode a specific resistance gene that inactivates the drug, and this gene can be transferred (process of conjugation) between isolates via cell-to-cell contact, so conferring this type of resistance in the recipient bacteria.

Foodborne pathogens can also occur in wild animals that are found in areas adjacent to urban populations. For example, seals that live in a Scottish estuary bordered by a city and towns have been shown to carry foodborne pathogens, namely Campylobacter. The seals most likely acquired the pathogen from sewage and wastewater contamination. Survey work is now underway to determine whether the seals also carry AMR genes and to characterise antibiotic resistant Campylobacter.

Benefits

SEFARI cover a wide scope of research on rural, agriculture and food issues connected with Antimicrobial resistance (AMR). A workshop brought together those working on distinct areas of AMR and Antimicrobial Use (AMU) across the SEFARI institutes and the wider stakeholder network, to aid in a more strategic, collective approach to tackling an urgent, global issue. Identified commonalities, e.g. in analytical or data gathering processes as well as in over-arching questions, will in turn help to facilitate the research processes and importantly, provides a wider perspective of AMR and AMU in Scotland. The workshop also identified knowledge gaps and raised some suggestions for how to address them going forward.

A key aspect was the inclusion of partner organisations to ensure that the work is relevant to Scotland’s policies on agriculture and food, and to regulatory requirements for food safety. Scottish Government representatives who fund the work and advise on animal health were included in the discussions, as well as food safety representatives from Food Standards Scotland. This helped to identify priority issues in AMR for Scotland that should be included in future strategic research.

In addition to mapping the scope of the work and identifying the key areas, we also identified that in this field, there is potential for confusion over the terminology. As such, we have also generated a glossary to cover the main terms.