Selection and Transmission of Antimicrobial Resistance in Complex Systems

Selection and transmission are key determinants for the dissemination of antimicrobial resistance (AMR) across the planet. These determinants of AMR are frequently studied in laboratory settings while in reality they occur in complex systems, e.g. in microbial communities that colonize human and animal guts or in environmental ecosystems. The central aim of STARCS (Selection and transmission of Antimicrobial Resistance in Complex Systems) is to characterize and quantify the processes of selection and transmission of AMR genes and drug-resistant bacteria in complex (eco)systems from a 'One Health' perspective and to integrate these elements into predictive mathematical models, which will be used to inform policy development.
STARCS will develop technological breakthroughs to assess selection and transmission dynamics on the level of the resistance gene, the mobile genetic element, the bacterium, the human-animal-environment interface and in clinical settings. This project will deliver important knowledge into selection and transmission of AMR, will provide the scientific community with novel tools to study selection and transfer of AMR in complex systems and will result in much-needed guidance towards policy decisions by international and national institutions. Ultimately the results from STARCS will form an evidence-based foundation for the development of new regulations, aimed at curbing the spread of
AMR.

The STARCS consortium will (i) develop and implement innovative metagenomic methodologies to map the expression of AMR genes and their linkage to bacterial hosts and mobile genetic elements in human, animal and environmental samples, (ii) use relevant animal models (using mice and ducks) and observational studies (in hospitals and in dogs and their owners) to analyse and quantify the processes of selection and transmission of drug-resistant Enterobacteriaceae (specifically Extended Spectrum Beta-Lactamase producing Escherichia coli) and (iii) implement state-of-the-art epidemiological modelling to quantify the spread of ESBL-producing E. coli between humans and animals. STARCS will develop technological breakthroughs to assess selection and transmission dynamics on the level of the resistance gene, the mobile genetic element, the bacterium, the human-animal-environment interface and in clinical settings. This project will deliver important knowledge into selection and transmission of AMR, will provide the scientific community with novel tools to study selection and transfer of AMR in complex systems and will result in much-needed guidance towards policy decisions by international and national institutions. Ultimately the results from STARCS will form an evidence-based foundation for the development of new regulations, aimed at curbing the spread of AMR.

The studies in STARCS will lead to important data that can be used to quantify the contribution of
animals and the environment in the burden of antibiotic resistant bacteria in humans. Specifically, the
mathematical modelling studies, informed by the empirical work in STARCS, aim to quantify the
projected health benefits in humans that could be achieved by substantial reductions in the usage of
antimicrobials in animals, or by reductions in exposure to resistance of animal origin. The results of this
project will enable STARCS to provide guidance towards policy decisions by (inter)national institutions
for new regulations aimed at minimizing the spread of AMR to humans from animal and environmental
sources. STARCS will meet this obligation by the ongoing contribution of its partners in national and
transnational multi-disciplinary fora on AMR and an active online presence (website, social media).
Manuscripts describing research funded by STARCS will be placed on preprint servers (e.g. BioRXiv)
upon submission for publication in a scientific journal, to enable rapid communication of scientific results.
Computational tools that are developed in STARCS will be made available through GitHub to facilitate
rapid adoption of these tools by the scientific community.
To facilitate knowledge transfer and generate synergistic interactions between partners, three meetings
for the STARCS consortium will be organized. These are planned for Q1 2017 (kick-off meeting) and Q2
2018 (mid-term meeting), and, finally, in Q4 2019, i.e. a few months before the conclusion of STARCS,
an international conference on the selection and transmission of AMR will be organized. This conference
will importantly contribute to the dissemination of the results of STARCS to the scientific community and
other stakeholders (e.g. health professionals, veterinarians, policy makers).