- Dynamics of Antimicrobial Resistance in the urban Water Cycle in Europe

In DARWIN, we will undertake a never-previously-performed pan-European examination of the fate of key AMR organisms and genetic determinants in Urban Water Systems (UWS) resulting from discharged hospital and community wastes, including transmission mechanisms in different stages of sewer catchments and receiving waters.

Background and aim
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. As AntiMicrobial Resistance (AMR) continues to expand new AMR mitigation approaches are urgently needed that go beyond just prudent antimicrobial use. Specifically, AMR will not be reduced until we understand all key drivers of AMR transmission, including human waste-born AMR disseminated via urban water systems. Urban AMR dissemination starts when one flushes the toilet and sewage flows into the sewer system.

AMR organisms and genes are enriched in the gut due to antimicrobial use and natural selection, but when gut bacteria enter the environment with faeces they are exposed to different environmental conditions with changes in temperature, richness of organic matter, redox conditions, and levels of antibiotics, metals, and biocides. While enteric bacteria tend to quickly die off in UWSs, this does not prevent dissemination of AMR genes to environmental strains with whom they comingle. Comingling is especially concerning where hospital and community wastes mix, such as in sewers. This mixing creates a major opportunity for Horizontal gene transfer (HGT) between faecal and non-faecal strains, and fuels the passage of AMR genes via environmental strains to the wider environment.

In this project, we will 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). 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.

The DARWIN team will by employing novel tools and methods evaluate bacteria that perform HGT within UWSs, and thereby identify ecosystem controls on AMR transmission, ultimately developing a predictive dynamic AMR model to guide risk assessments and sewage management decisions. This will have significant implications on monitoring resistance and minimize the release or introduction of AMR in the environment as well as the human exposure to them.

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