Dynamics of Antimicrobial Resistance in the Urban Water Cycle in Europe




Research Project: 2017-01-01 - 2019-12-31
Total sum awarded: €1 667 970

While therapeutic antibiotic use directly impacts the evolution of AntiMicrobial Resistance (AMR), it has become increasingly clear that the environmental dimension of AMR is also of great importance. We postulate that urban water systems (UWS), which are our receptacle for excreted antimicrobials, AMR organisms and AMR genes, are central conduits of AMR to and from pathogens and environmental strains. This is because of high microbial densities and the co-mingling of different wastes, which promotes accelerated AMR gene transfer (HGT) and multi-resistance due to the cooccurrence of antibiotics, biocides, metals and microbes. In DARWIN, we will undertake a never-previously-performed pan-European examination of the fate of key AMR organisms and genetic determinants in UWSs resulting from discharged hospital and community wastes, including transmission mechanisms in different stages of sewer catchments and receiving waters. We focus on the spread of AMR genes encoding clinically relevant extended spectrum β-lactam (ESBL) and carbapenem resistance in three countries with differing AMR profiles and sewage management practices. We postulate that AMR genes readily transmit in UWSs from pathogens and commensal hosts in human wastes (after antibiotic use) to environmental strains better adapted to migrate through the sewer environment, which is driven by local ecologies, conjugal plasmid transfer and phage-mediated transduction. Hence, we will, for the first time, determine specific bacterial hosts that carry AMR genes across UWSs, and identify where key HGT events occur with the ultimate goal of assessing the relative risk of AMR genes returning back to humans due to environmental exposure. To guide risk assessments, a predictive dynamic mathematical model for UWSs will bedeveloped to assist in health and sewage management decisions.

Read More
Read Less
  • Barth Smets, Technical University of Denmark, Denmark (Coordinator)
  • Søren Johannes Sørensen, University of Copenhagen, Denmark (Partner)
  • David Graham, Newcastle University, United Kingdom (Partner)
  • Jan-Ulrich Kreft, University of Birmingham, United Kingdom (Partner)
  • Jesús L. Romalde, Universidade de Santiago de Compostela (USC), Spain (Partner)
  • Carlos García-Riestra, University Hospital Complex of Santiago de Compostela, Spain (Partner)
  • Mical Paul, Technion Israel Institute of Technology, Israel (Partner)

There is mounting concern that wastewater systems, which receive antibiotic residues and antibiotic resistant organisms and their antibiotic resistance genes, could facilitate the environmental dissemination of resistance. DARWIN has examined the fate of clinically relevant antibiotic resistances along sewer catchments and receiving waters in three European cities. We found that hospitals sewers contain higher concentrations of resistant bacteria than sewers in residential areas. Many of the resistance genes, and especially those in hospital wastewater, were carried on genetic elements that have potential to transfer rapidly from one bacterium to another. We collected several other indications of the potential for microbial communities in wastewater systems to exchange resistance genes, yet we did not find direct evidence of such transfer, possibly because of the difficulty of the task (enormous amounts of bacteria transit across sewers and wastewater treatment plants). Overall, our data suggests that our wastewater collection and treatment systems discharge only few antibiotic resistant organisms and genes in the environment but the question of the impact of this low-level pollution remains unanswered. We proposed a standard way for scientists to report their findings to facilitate data interpretation and reuse and built mathematical models to understand the dynamics of antibiotic resistance that will contribute to further development of mitigation strategies. Impact of the study: DARWIN, through the obtained evidence and through its partners, has significantly contributed to wider efforts aimed at mitigating the spread of antibiotic resistance around the world. Such involvement has included science-informed public information on AMR (e.g., an invited Insights piece for the Conversation), co-authoring international recommendations for the World Health Organisation aimed at promoting local National Action Plans and socio-technical AMR mitigation options for countries around the world. We also co-wrote guidance for the Wellcome Trust and US Centre for Disease Control and Prevention on essential initiatives to mitigate AMR; have been invited input providers to the USA PACCARB (Presidential Advisory Council on Combating Antibiotic Resistant Bacteria); and are members of the technical advisory council of ICARS (International Centre for Antimicrobial Resistance Solutions).