By its very nature then, AMR is a One-Health problem which requiring integrative interdisciplinary solutions, as well as being one of the largest current health threats that humanity faces. It impacts the ability of healthcare to function normally, and in developing countries it undermines already weakened healthcare systems.
Professor of Molecular Bacteriology at the School of Cellular and Molecular Medicine, Matthew Avison was the Elizabeth Blackwell Institute’s Bristol AMR Research Strand lead. He explains: “The Bristol AMR community had already committed to an interdisciplinary approach – thanks to funding from the Wellcome Trust, the Elizabeth Blackwell Institute’s AMR Research Strand was started with the aim of bolstering these efforts. Prior to the establishment of the Strand, AMR research in Bristol already operated in interdisciplinary pockets.
“The aim of the Strand was initially to facilitate ways in which the diverse AMR research community could come together to compete for future large-scale research funding. This would cement the University’s place as the UK centre of excellence for interdisciplinary AMR research and could make a real impact on global health.”
As the Strand was coming into a space with existing multidisciplinary research, it was able to hit the ground running, contributing to a wide variety of novel, nascent or existing projects; locally, nationally or internationally.
Interdisciplinary by design
Before the Strand was started, AMR research in Bristol was already working within a One Health multidisciplinary framework, thanks in part to previous funding by the Engineering and Physical Sciences Research Council’s ‘Bridging the Gaps’ programme (BristolBridge) led by Professor Adrian Mulholland. One of Professor Avison’s focusses with the Bristol AMR strand was to work with Professor Mulholland to refine and amplify the extant collaborative processes, as well as identifying new opportunities."
“One of the key things we’ve been able to do includes bringing clinicians into multiple research areas - linking their knowledge with other data streams, such as genomic surveillance data, and we’ve been able to demonstrate the importance of AMR research to younger clinicians. I think the Strand has built a kind of clinical science interface community in this area, which I think will stand us in good stead both in Bristol and generally in the country.”
Other work within the Strand involved continuations of pre-existing One Health strategies in lower-middle-income countries, which is likely to have substantial future impact, as Professor Avison explains:
“One of Bristol AMR’s achievements, thanks to funding from the UK Research Councils, is to show that the primary reason for the AMR increases is interactions between humans - particularly in a healthcare environment, where people can spread resistant bacteria between each other.”
This contradicts inaccurate assumptions in some corners of the media, and increasingly in the general populace, which suggests that the AMR issue in humans is in large part caused by the prophylactic over-use of antibiotics in livestock.
Professor Avison expands: “One of our studies is recently complete, but the preliminary model has already been published. It shows quite clearly, in Thailand, the importance of human antimicrobial usage relative to animal antimicrobial usage. And in fact, one of the main things we found is that the farmers - at least in Thailand - are not using antimicrobials to the levels that everybody assumed they would be, partly because they cost a lot."
“We’ve also had incredibly good buy-in with UK farmers; they want to show UK farming practices in the best possible light, of course, but they also really want to get involved and they want to learn. We've done a number of projects on UK farms, and we’ve recently started a huge project funded by the Welsh Government to look at farming systems in Wales and the levels of antibiotic usage and resistance, what does that do to antibiotic resistance in humans and so on. All of this off the back of the success we've had with other projects in England and overseas. We have another similar nascent project in Argentina, for example.
“One of the things the strand was able to do was enhance the reach of a given project, which gave us a greater chance of success at gaining further funding to expand the work, and enhanced awareness and publicity. We can use our understanding of these AMR drivers to inform and educate policymakers in other countries - so we can try to bring down the increasing rates of bacterial AMR resistance around the world.”
Funding global challenges
Another project with substantial strand input involves the clinical implementation of diagnostics. One of the extant Bristol AMR objectives was to translate novel technologies or intellectual property into clinical practice.
Part of this focused on refining antibiotic prescription methodologies - giving the right drug to the right person at the right time. “This incorporates diagnostics, behavioural sciences and other push and pull factors that involve instigating change at patient and caregiver levels, and pooling them all together,” said Professor Avison.
“I think that's part of the legacy of our Bristol AMR Research Strand, the ability to take disparate areas of research, integrate them and run with the result, making this type of interdisciplinary project possible.”
Buying time
Global issues such as the AMR problem, of course, require such flexibilities, and a multiplicity of approaches. The presence of resistant organisms requires a change in established approaches; in our practices - and much like lockdowns in the COVID-19 pandemic, such changes in behaviour can also serve to buy time to develop new treatments and protocols for previous intractable infections. But it turns out that the organisms themselves might actually be able to help, if we give them enough time; some bacteria actually lose antibiotic resistance if you reduce the antibiotic levels enough, for long enough, as other competitive factors in their life cycle and environments take over.
“This is true for MRSA, for example,” says Professor Avison. “It’s one of the main reasons why MRSA rates have fallen in the UK. It’s not only about cleanliness or more people washing their hands - it’s really an ecological battle that's been happening between antibiotic resistant MRSA, and MSSA, which is susceptible. MSSA has pushed MRSA out of the environmental niche, as it prospers more readily in the antibiotic’s absence. People are still getting infections, but the infections are susceptive to the treatments.
Therapeutics riding shotgun
However, time alone isn’t going to be sufficient to sort out the problem. Another approach taken by the Bristol AMR Research Strand’s effort involves using different compounds administered alongside antibiotics to effectively shut down the pathogen’s resistance to them – including collaborative research which was recently published in Nature Chemistry.
“This is an area in which Bristol AMR is very strong,” said Professor Avison. “But the Strand once again was key in generating the interface between clinical data, genomics and diagnostics needed - so that in the future we’ll be able to use this tripartite expertise and the existing the technology to continue this into a clinical setting. There’s very real promise down this avenue.”
COVID’s silver lining
Of course, the pandemic has clearly interfered with the work that the Bristol AMR Research Strand has been doing, but it has perhaps had other more positive effects.
The sudden thrusting of the world into a crisis situation has, perhaps paradoxically, brought some benefits to AMR research. Having infectious diseases writ large in the public consciousness can only be of benefit when it comes to awareness, interest, and education about related topics such as AMR. Moreover, the swift and comprehensive data analysis that the pandemic required - the integration of track and trace data through to viral genomic sequencing and environmental analysis - will be capitalised upon for AMR research.
“An awful lot of public health infrastructure will be leftover at the end of the pandemic, which we can use to look at AMR. So, a lot of the genomic surveillance set up for COVID could be for AMR surveillance, alongside new clinical data linkage approaches”.
The Bristol AMR initiative’s involvement with this is primarily around finding ways to tie all the disparate data strands into one manageable whole, to understand which patients are most at risk from a resistant infection, and why. Here, again, the Strand’s focus came into play.
“We’ve had some great success in that area - we've been able to get funding to link together primary care data from GP practices with secondary hospital data and the microbiology lab diagnostic data, to try and follow patients through the maze and see where they're potentially risk from picking up these resistant organisms,” said Professor Avison.
In future, then, this work will help to stratify patients and predict which ones are going to be most at risk, so that clinicians and health care workers can find ways to reduce patients’ exposure to resistant organisms.
Public engagement
In November 2019, the AMR Strand hosted the Colston Research Society Symposium, a 2-day international symposium with around 700 attendees. Speakers from 4 continents spoke on the current progress across a whole spectrum of approaches. Part of the symposium was filmed by BBC Points West, who also conducted interviews with luminaries including Prof Avison.
However, the following year, pandemic-related lockdowns curtailed many planned ‘in person’ activities which engaged with the public - a strand-led project with the Bristol Museum and Art Gallery had to be abandoned, for example, among many other abandoned projects across the university which fell by the wayside. But other, more remote projects have still found their way through.
“I advised on a series of well-received Young Adult novels by Virginia Bergin about a dystopian pandemic and its aftermath (this was all pre-COVID),” said Professor Avison, “And we've also been involved in BBC Radio dramas. Joanna Coast, Professor in the Economics of Health & Care, advised on a Radio 4 drama about AMR, set in a near-future in which doctors can no longer prescribe effective antibiotics. So, we’re slowly pushing AMR into popular culture."
Ultimately, the legacy of the AMR strand is suggested by the interest taken in its activities - and that of the AMR group as a whole - by larger administrative bodies. The strand’s interdisciplinary work and focus has been taken as a model by the GW4 Alliance - a consortium of four of the most research-intensive and innovative universities in the UK: Bath, Bristol, Cardiff and Exeter. The GW4 Alliance has made AMR one of their three strategic funded priority areas along with other societal challenges, Climate and Net Zero.
“They’ve taken what we've done as an exemplar and decided to replicate that within the other universities and bring it all together,” said Professor Avison. “The AMR project, and the Strand have shown what can be done when you come together within one University, and we’ve given signposts as to how to move forward, as a region, to combat a problem that will impact everyone.”