Dynamics of Antimicrobial Resistance in the Urban Water Cycle in Europe

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Resistance of pathogenic bacteria to antibiotics and other antimicrobials is increasing everywhere on Earth. This is making progressively our current antibiotics useless, potentially placing patient's lives at risk as some can no longer be treated by available treatment options. Resistance is not only selected inside the human body when antibiotics are used to treat people, but also selected after the antibiotics from patients in hospitals or ill people at home are entering the sewage. Moreover, the resistance genes can transfer to other bacteria, where they can persist and eventually transfer back to pathogenic bacteria. This transfer also happens in the sewage. We postulate that urban water systems, that is, sewers, sewage treatment plants and receiving waters, are central places of exchange of resistance genes between pathogenic bacteria and environmental bacteria because these systems continuously receive excreted antimicrobials, resistant bacteria and resistance genes from many sources. Further, the high numbers of bacteria in these systems increases the transfer of resistance genes between different bacteria. The mixing of different wastes (e.g., hospital and community sewage) increases the selection for bacteria carrying multiple resistance genes due to the simultaneous presence of various antibiotics, biocides, and heavy metals.DARWIN (Dynamics of Antimicrobial Resistance in the Urban Water Cycle in Europe) will be the first project to perform a cross-European examination of the fate of key resistant bacteria and resistance genes in UWSs resulting from discharged hospital and community wastes, including mechanisms of resistance gene transfer in different stages of sewer catchments and receiving waters. We will focus on the spread of resistance genes that are amongst the most problematic now because they confer resistance to the latest generation of antibiotics available (genes for extended spectrum beta-lactamases (ESBL) and carbapenemases). Specifically, we will investigate these resistance classes in three countries that differ in their use of antibiotics and sewage management practices: Denmark, Spain and the UK. We postulate that resistance genes readily transmit in urban water systems from pathogenic and non-pathogenic "gut" bacteria in human wastes (after antibiotic use) to environmental bacteria better adapted to the sewer environment. The environmental bacteria then carry the resistance genes across the wider environment, increasing community exposure. Hence, we will, for the first time, determine which specific bacteria carry the resistance genes across the urban water systems and identify where resistance gene transfer events occur. Our ultimate goal is to assess the relative risk of resistance genes returning back to humans due to environmental exposure. To guide risk assessments, a predictive dynamic mathematical model for the urban water systems will be developed to assist in health and sewage management decisions.