Stemming the tide of AMR in the natural environment.

The hidden threat: AMR in our waters

The environment is a reservoir of antimicrobial resistance (AMR). AMR is a natural process, evolved over millions of years to counteract antimicrobials that are produced by microorganisms, some of which we have modified to use as lifesaving drugs.  

The environment is further enriched with AMR bacteria and antimicrobials present in human and animal waste. When we take a dip in our rivers or the sea, we are swimming in water that often contains antimicrobial resistant bacteria which we can ingest.

The prevalence of AMR in human-impacted environments starkly highlights the complex cycle of antimicrobial use and spread of resistance. When we take antimicrobial drugs, we excrete around seventy per cent of these medicines through our bodies into sewers¹², along with faecal bacteria which may already carry resistance mechanisms. Wastewater treatment plans remove billions of human faecal bacteria, some however, still find their way into our waterways. This is also true of animal waste. In fact, the majority of antimicrobials produced globally are used in agriculture and fish farming, further contributing to the release of antimicrobial compounds into the environment. 

In natural waters, resistance may evolve where antimicrobials, excreted by humans and animals, are above a selective threshold that favours the survival of resistant bacteria. These can then find their way back into our bodies, for example by being ingested when we eat contaminated food or swim in the sea. University of Exeter research has led to new understanding and has informed action on this dangerous cycle. Findings include identifying who is most at risk, and what concentrations of antibiotics are unsafe in our waters and could trigger the evolution of resistance. Exeter’s One Health research approach combines a wide range of expertise to address this complex issue from multiple angles. 

Professor William Gaze, Professor of Microbiology at the University of Exeter Medical School’s European Centre for the Environment and Human Health, said “The problem of AMR covers every aspect of life and science, creating health and economic impacts globally. For example, higher temperatures associated with climate change may lead to increased survival of human gut bacteria in the environment and increased flooding will increase transmission through human exposure to polluted water.

"We have to take a broader holistic view to see how all the different elements of AMR relate to each other, including the contribution of natural and farmed environments. Our group is unique, in that we look at the combination of AMR evolution, the spread of AMR within the environment, and finally the impact of environmental transmission on human health. This highly unusual approach gives Exeter the ability to undertake joined-up thinking to tackle the problem.”

Professor Gaze’s expertise in AMR emerges from his background as a marine biologist investigating microorganisms in freshwater and deep-sea marine systems, before focusing on AMR nearly 20 years ago. He is also an active member of movements to combine research disciplines to tackle AMR, and to unite researchers, stakeholders and policy makers.

In one strand of work, Professor Gaze and the team look at whether the very low concentrations of antibiotics found in our waters can drive resistance. To analyse the complex communities of the billions of bacteria that are found in every single gram of sediment or soil, they use tools including metagenomics. After extracting DNA, they sequence a sub-sample of the genomes and characterise the resistance genes. They also apply quantitative Polymerase Chain Reaction (PCR) – which was widely used in diagnosing COVID-19 infection. This allows them to calculate the prevalence of AMR in environmental communities of bacteria. 

Dr Aimee Murray and colleagues found that the antibiotic ciprofloxacin poses a high risk of driving resistance selection, even at the low concentrations at which it can be found in the environment.  

Using ciprofloxacin data generated at Exeter combined with data collected by the UK water industry, the team found that ciprofloxacin was at sufficiently high concentrations to drive selection for AMR in 90 per cent of untreated wastewater, and around 45 per cent of treated wastewater samples tested. In research raised in the House of Lords, the team estimated this might translate to high enough concentrations to risk selection in around three per cent of rivers and other surface waters that receive the treated wastewater.

The team also found that the antibiotic trimethoprim drives resistance at concentrations found in the environment. This antibiotic has subsequently been added to the Water Framework Directive’s Hazardous Compounds Watch List of chemicals that may pose a threat to environmental or human health. If more evidence emerges, limits could be imposed on the environmental discharge of these antibiotics.

Dr Murray is expanding the research area to include other environmental pollutants, and complex mixtures of antimicrobial pollutants in a NERC New Investigator grant. Additionally, Dr Murray and colleagues are also researching how co-contamination of environments with antibiotics and microplastics might impact AMR and how resistant pathogens on microplastics may enter the food chain.

Working with the campaign charity Surfers Against Sewage, Dr Anne Leonard conducted the Beach Bums survey, in which surfers were asked to take rectal swabs for analysis. Surfers were chosen as they’re known to swallow more water, and therefore more bacteria, than regular swimmers. The team found that surfers were more than three times as likely to carry resistant E. coli in their guts than non-swimmers.

“Carrying antibiotic resistant bacteria in your gut could potentially lead to infections which are difficult to treat. People may not display any symptoms when colonised, but they might suffer from infections in the future or pass on the resistant bacteria in their guts to other people, who may be more vulnerable.” - Dr Anne Leonard

This high impact work influenced policy and was cited by both the UK Government and World Health Organization and has led to the Poo-Sticks project,  which over the summer collected over 300 fecal samples from freshwater wild swimmers to understand more about how AMR bacteria enter our bodies. This project builds on our previous work and aims to inform strategies for reducing the spread of AMR.

To understand how AMR bacteria behave in our waters, the team has also analysed whole river systems. In rivers, resistant bacteria are present at dramatically varying rates, which is dependent on how far away the nearest wastewater treatment plant is, how large it is and what type of treatment happens there. “This tells us that we’re having a really major impact on the level of AMR in our environments,” said Professor Gaze. “Understanding this helps us think about mitigation strategies.”

The team has a strong partnership with the Environmental Agency. For years, they have analysed samples of Escherichia coli (E. coli), bacteria naturally found in the gut of humans and animals, which are used as a marker of water quality in natural bathing waters. Dr Anne Leonard and Dr Lihong Zhang expanded upon this work, by looking specifically at the risk of human exposure to resistant E. coli bacteria. Dr Leonard is now extending this work to use of rivers for wild swimming and through shellfish consumption.

For the next step, Dr Leonard, Professor Gaze, Professor Tim Taylor and Dr Aimee Murray are working on AMR in coastal waters through a £9 million Horizon Europe grant called BlueAdapt. This project has collaborators in Bangor University and many institutions across Europe and is investigating the impact that climate change may have on bacteria and associated health risks. Further work on AMR and climate change at Exeter is being undertaken by Dr Dan Padfield (NERC Fellow).

The group’s research has had a number of policy influences in the UK, the EU and internationally. Professor Gaze has worked with the United Nations Environment Programme, co-authoring a report on AMR, coinciding with a commitment to tackle the issue from an environmental and health perspective. Professor Gaze works with Defra and the EA through a knowledge exchange programme which also brings in the pharmaceutical industry and the water industry. A recent AMR network grant focusing on the impacts of climate change on AMR includes project partners from all sectors, representing an exciting shift from conducting fundamental research to applying that research and working with policy makers and stakeholders to find solutions.