Antimicrobial resistance in the environment

The Microbiology Society is undertaking a project entitled A Sustainable Future as part of our 75th Anniversary, which aims to highlight the Sustainable Development Goals (SDGs) to our members and empower them to use their research to evidence and impact the goals. Earlier this year, we put a call out to our members to submit case studies in the following three areas: antimicrobial resistance, soil health and the circular economy.

This case study is written by Dr Aimee Kaye Murray, who is a NERC Industrial Innovation Fellow and proleptic lecturer at the University of Exeter Medical School and a member of the Microbiology Society. It focuses on antimicrobial resistance; a naturally occurring process, whereby micro-organisms (bacteria, viruses, fungi and parasites) can change and adapt over time, either by modifying the target of the antimicrobial, or by developing and exchanging resistance genes.

Antimicrobial resistance (AMR) is one of the most significant threats to society. The One Health approach considers all aspects of AMR including clinical, farmed and ‘natural’ environments. However, the natural environment (for example, rivers and streams), though heavily impacted by human activities, is still the least well studied.

For example, 11 billion litres of wastewater are treated every day in the UK. Wastewater contains active antimicrobial compounds such as antibiotics, which can promote the evolution of AMR. Research has shown that these low concentrations of antibiotics are enough to increase levels of AMR in laboratory experiments. Our research with AstraZeneca has gone further to show that this occurs in complex communities of bacteria derived from sewage and that low, environmentally relevant concentrations of one clinically important antibiotic can even increase levels of AMR to the same extent as clinically relevant concentrations [1].

This evidence demonstrates the environment is important, but the release of antibiotics and antimicrobials into the environment is not currently regulated. Regulation requires evidence that antibiotics at environmental concentrations pose a risk, but current experimental methods only look at the toxicity risk antibiotics pose to aquatic organisms, rather than focusing on AMR.

Therefore, my NERC Industrial Innovation Fellowship aimed to develop the first experimental method that could be routinely used for environmental risk assessment of antibiotics to establish if threshold concentrations of antibiotics are needed in wastewater. I called this the SELECT method (which stands for SELection Endpoint in Communities of bacTeria), and it was recently published in Environmental Health Perspectives [2]. We showed the growth based SELECT method is a reliable proxy for selection for key AMR marker genes in wastewater communities, and that several antibiotics may pose a selection risk in wastewater, particularly ciprofloxacin and trimethoprim. These data were considered during the selection process for antibiotics that were included on the European Union’s Commission Water Framework Directive Watch List in 2020 [3].

Following interest in our previous work with AstraZeneca on macrolides by the media, we were contacted by the British Society for Antimicrobial Chemotherapy (BSAC) and All-Party Parliamentary Group (APPG) for Antibiotics secretariat [4]. We wrote a blog for BSAC and then presented the SELECT method to the APPG late November with the view to inform amendments to the new Environment Bill, due to pass through the House of Lords late 2020/early 2021 [5,6]. Currently, there is no mention of AMR or antibiotics in the Environment Bill, despite commitments to adopt a One Health approach outlined in the UK 5-year national action plan to combat AMR [7]. Acknowledgement of AMR and antibiotics in the environment, and in the Environment Bill would be a first step towards the regulation of environmental antibiotic residues in the UK.

In future, we aim to fully validate the SELECT method as a test that can be used routinely in the UK and beyond, to perform environmental risk assessment of antibiotics in terms of their potential to select for AMR. We also plan to adapt the SELECT method for use in environmental surveillance, to identify hotspots of resistance selection that would enable targeted mitigation. The SELECT method is particularly well suited for this in lower- and middle-income countries, as it is very low cost and requires minimal lab equipment. A further SELECT application includes prioritising new antimicrobial compounds on the basis of their selective profile, at early stages in the drug discovery pipeline. I will present SELECT to the AMR Industry Alliance to discuss this idea early 2021 [8]. Together, our research and its potential influences on policy can contribute to a sustainable future by helping secure ‘clean water and sanitation’ (SDG 6), ‘good health’ (SDG 3) and ‘responsible consumption and production’ (SDG 12) of antibiotics. The SELECT method could also help ‘reduce inequality’ (SDG 10) by providing a low-cost option in future for environmental surveillance of AMR in lower- to middle-income countries.

References

[1] Murray AK, Zhang L, Yin X, Zhang T, Buckling A, Snape J, Gaze WH. Novel insights into selection for antibiotic resistance in complex microbial communities. MBio. 2018 Sep 5;9(4):e00969-18. https://doi.org/10.1128/MBIO.00969-18

[2] Murray AK, Stanton IC, Wright J, Zhang L, Snape J, Gaze WH. The ‘SELection End points in Communities of bacTeria’(SELECT) Method: A Novel Experimental Assay to Facilitate Risk Assessment of Selection for Antimicrobial Resistance in the Environment. Environmental health perspectives. 2020 Oct 21;128(10):107007. https://doi.org/10.1289/EHP6635

[3] European Commission. Selection of substances for the 3rd Watch List under the Water Framework Directive. https://publications.jrc.ec.europa.eu/repository/bitstream/JRC121346/third_watch_list_report_pdf.pdf

[4] Stanton IC, Murray AK, Zhang L, Snape J, Gaze WH. Evolution of antibiotic resistance at low antibiotic concentrations including selection below the minimal selective concentration. Communications biology. 2020 Sep 3;3(1):1-1. https://doi.org/10.1038/s42003-020-01176-w

[5] British Society for Antimicrobial Chemotherapy. Antibiotics and antibiotic resistance in our waters – are we up a creek without a paddle? https://bsac.org.uk/antibiotics-and-antibiotic-resistance-in-our-waters-are-we-up-a-creek-without-a-paddle/

[6] APPG on Antibiotics. Antibiotic residues in sewage and agricultural run-off: can we determine safe thresholds to combat deadly superbugs? https://appg-on-antibiotics.com/assets/Report-APPGMeeting2020-16122020.pdf

[7] HM Government. UK 5-year action plan for antimicrobial resistance 2019 to 2024. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/784894/UK_AMR_5_year_national_action_plan.pdf

[8] AMR Industry Alliance. Responsible manufacturing. https://www.amrindustryalliance.org/shared-goals/common-antibiotic-manufacturing-framework/

About the author

Dr Aimee Kaye Murray is a Natural Environment Research Council (NERC) Industrial Innovation Fellow and proleptic lecturer at the University of Exeter Medical School, European Centre for Environment and Human Health and the Environment and Sustainability Institute in Penryn, Cornwall, UK. Find out more about her research here.