Detecting Antimicrobials and Resistance in the Environment (DARE)

A toolkit for tracking antimicrobials and the emergence of AMR in the environment. The DARE solution will use integrated “omics” technologies to detect antimicrobials used in human and animal health, and agriculture within the environment and their impact on functional diversity and AMR in aquatic microbial communities.

Prof Rosemary Dorrington

Rhodes University, Makhanda, South Africa

Antimicrobials undergo rigorous evaluation including ADME (adsorption, distribution, metabolism, and excretion), preclinical pharmacokinetics, pharmacodynamics and toxicity before progressing to human clinical trials and approval for clinical use. The mechanisms of resistance in clinical isolates of the target pathogen(s) are also extensively scrutinized to predict the potential emergence of AMR in the patient. In contrast, we know almost nothing about the fate of antimicrobials after they are released (post patient) into the environment via wastewater treatment plants and agricultural runoff.

Human, animal and plant health are inextricably linked to ecosystem health in the environment (One Health). Microbial communities are the engine rooms of ecosystem functioning and a reservoir for AMR, therefore understanding how antimicrobials impact microbial community diversity, metabolism and the development of resistance is a critical component of effective management strategies for combating AMR in bacterial and fungal pathogens. 

Gaps in our knowledge 

(1) How long do antimicrobials persist in the environment and where are they retained? 

(2) How are antimicrobials metabolised in the environment and are these metabolites bioactive?  

(3) How do microbial communities respond to the presence of antimicrobials and their metabolites? 

(4) How do antimicrobials promote the incidence of AMR within impacted ecosystems?

Importance to the local community (Albany district)

We will leverage existing Rhodes University programmes to engage with local and provincial healthcare role players. Members of the DARE team are well placed to facilitate engagement with the farming and conservation community. 

The Kowie system is located within the Amatole water source area, where a significant number of households rely on rivers, springs and boreholes for drinking water for household use and subsistence livestock. Identification of AMR hotspots will inform the Makana  and Ndlambe Municipalities, subsistence stock farmers, commercial agriculture and wildlife conservation programmes to manage the risk of AMR spread. 

Impact on National Policy development

The DARE data will feed into the development of the South African Antibiotics Stewardship (AMS) Programme, supporting the development of AMS policies (South African National Departments of Health (human) and Agriculture Land Reform and Rural Development (animal and plant). The DARE data will also influence water quality policy development through SAEON, the South African National Department of Water and Sanitation and the Water Research Commission

Impact on the broader scientific community

Our intention is to make the DARE toolkit publicly available to allow roll out of this surveillance approach beyond the borders of South Africa.

Within the Eastern Cape, the Albany Biosphere is acknowledged as a region of global biodiversity significance with six of seven terrestrial biomes and exceptional species richness. In the marine environment there are two ecologically sensitive marine protected areas (1600 square km) within 40 km of the Kowie mouth. Despite an abundance of biodiversity, the Eastern Cape is South Africa's poorest province, with 12.7 % of the population living in poverty and a 40 % unemployment rate (The South African Gateway, updated 20/10/2023). There has been a concerted effort to derive socio-economic upliftment from rewilding and biodiversity restoration in line with track 6  of the One Health Joint Plan of Action (2022-2026) Integrating the environment into One Health. Central to this is an initiative to develop a network of contiguous conservation landscapes that connect the Addo Elephant National Park to the Great Fish River Nature Reserve (the Albany Biodiversity Corridor Project), achieving socio-economic beneficiation via the restoration of connectivity & functional ecosystems as the driver of a nature-based economy.  

The Kowie and its tributaries are at the heart of the Albany corridor and therefore the DARE project will contribute to developing One Health approaches to rewilding and restoration efforts.

The direct outcome of this project will be the identification of AMR hotspots along the Blaauwkrantz and Kowie rivers that will allow the Makana and Ndlambe  Local Municipalities, subsistence stock farmers, commercial agriculture and local wildlife conservation programmes to manage the risk of AMR. 

Our solution provides the eADME that is currently the missing information that is needed for an effective Antimicrobial Stewardship programme. Specifically, our primary data will provide information on the persistence and retained activity of antimicrobials in the environment to inform the development of strategies for antimicrobial use and -stewardship.

We will disseminate our results through peer-reviewed publications. The DARE Toolkit will be accessible through a free to use dashboard, providing reference datasets, protocols and data analysis pipelines. In addition, we will build capacity by offering in person and in silico training workshops on data analysis to roll out the technology for routine AMR surveillance of waterways.

In Year 1 we will focus on assemblingreference libraries and methods development and stakeholder. We will host a series of stakeholder workshops to establish a forum for stakeholder groups to engage with the project. These workshops will provide opportunities for promoting public awareness of One Health and AMR. They will serve to bring on board landowners to contribute to the Proof of Concept study.

In Year 2 we will complete our Proof of Concept study on the Kowie and Blaauwkranz in Q4 (Milestone 4 and 5). This will provide us with information on the presence of antimicrobials and potential AMR hotspots that will be made available to local and regional stakeholder groups at a series of workshops planned for Q4 of this year. We will have a broader impact by publishing our data in peer reviewed journals during year 2.

Following a successful proof of concept study, we plan to expand our surveillance activities to include other important river systems impacted by urban settlements and commercial agriculture e.g. the Sundays and Swartkops rivers in the vicinity of Algoa Bay. This area is a SAEON Sentinel site for Long Term Socio-Ecological Research (LTSER) on climate change.

1. Completion of the DARE Reference library of clinically approved antimicrobials used in Makhanda (end Q2, year 1)

2. Assembly of the DARE Reference library of MS/MS data and retained bioactivity of metabolites derived from clinically approved antimicrobials in laboratory experiments (end Q4, year 1)

3. Identification of indicator microbial species and AMR genes in laboratory metabolism experiments (end Q2, year 2)

4. Survey of antimicrobial presence, distribution and persistence in the study site (Y2, end Q4)

5. Identification of AMR hotspots in the study site (Y2, end Q4)

6. Synthesis of Proof-of-Concept study and Final Report (Y3, end Q4)

7. Peer-reviewed publications (Year 2 and Year 3) and a policy white paper (end year 3)

No significant barriers to be overcome

This concept has the potential to answer a number of unknowns regarding the impact of antimicrobials on the environment and subsequent promotion of AMR mechanisms that are introduced into the microbial reservoir of resistance genes. While our primary aim is to apply for funding to support the project, we are interested in tapping into the the experience of the Trinity Challenge network for assistance with the roll-out of surveillance programs outside of South Africa and to promote the consideration of the study's findings for implementation of an AMS programme.

Announcement of the call by the South African Medical Research Council