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.
To reach this goal, the consortium will (i) develop and implement innovative metagenomics 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 humananimalenvironment 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
- Rob Willems, University Medical Center Utrecht, Netherlands (Coordinator)
- Dik Mevius, Wageningen University & Research, Netherlands
- Dan Andersson, Uppsala University, Sweden
- Teresa M Coque, Ramón y Cajal University Hospital, Spain
- Romain Koszul, Pasteur Institute, France
- Mark Woolhouse, University of Edinburgh, United Kingdom
- Surbhi Malhotra-Kumar, University of Antwerp, Belgium
ESBL-producing Enterobacteriaceae (ESBL-PE) are not new, having first been recognised in the 1980s. However, since 2003, the CTX-M type of ESBL have been constantly increasing and rapidly spreading. Most CTX-M-producing Enterobacteriaceae are exceptionally resistant to multiple antibiotics. These include penicillins and cephalosporins, two of the most important and widely used antibiotics. As a result, there are very limited treatment options for mild to moderate infections, which makes it of pivotal importance to control the emergence and spread of ESBL-PE.
In the STARCS project we study he pathways by which resistant bacteria, particularly ESBL-PE, can emerge in complex ecosystems, in which they can acquire genetic material that encodes resistance to antibiotics. To this aim, we have developed a number of tools that are used to characterise the reservoir of resistant bacteria in microbial ecosystems. In addition, we perform research into the transfer of resistant bacteria between animals and humans. Among other things, we study whether resistant bacteria can be transferred between dogs and their owners.
- Genome Medicine, 2021. Mode and dynamics of vanA-type vancomycin resistance dissemination in Dutch hospitals.
- Bioinformatics, 2020. gplas: a comprehensive tool for plasmid analysis using short-read graphs
- bioRxiv, 2020. Genomic rearrangements uncovered by genome-wide co-evolution analysis of a major nosocomial pathogen Enterococcus faecium
- Front. Microbiol, 2020. Antibiotic Resistance: Moving From Individual Health Norms to Social Norms in One Health and Global Health
- bioRxiv, 2019. Genomes of a major nosocomial pathogen Enterococcus faecium are shaped by adaptive evolution of the chromosome and plasmidome
- Environmental Microbiology, 2019. Phylogenomics of Enterococcus faecalis from wild birds: new insights into host‐associated differences in core and accessory genomes of the species
- Environment International, 2018. Wild corvid birds colonized with vancomycin-resistant Enterococcus faecium of human origin harbor epidemic vanA plasmids
- Environmental Microbiology Reports, 2018. Long‐term carriage and rapid transmission of extended spectrum beta‐lactamase‐producing E. coli within a flock of Mallards in the absence of antibiotic selection
- F1000Research, 2018. The challenges of designing a benchmark strategy for bioinformatics pipelines in the identification of antimicrobial resistance determinants using next generation sequencing technologies
- Foodborne Pathogens and Disease, 2018. Are Food Animals Responsible for Transfer of Antimicrobial-Resistant Escherichia coli or Their Resistance Determinants to Human Populations? A Systematic Review
- Microbial Genomics, 2018. mlplasmids: a user-friendly tool to predict plasmid- and chromosome-derived sequences for single species
- Microbiome, 2018. In-depth resistome analysis by targeted metagenomics
- Nature Microbiology, 2018. Prediction of the intestinal resistome by a three-dimensional structure-based method
- Science of The Total Environment, 2018. Water supply and feed as sources of antimicrobial-resistant Enterococcus spp. in aquacultures of rainbow trout (Oncorhyncus mykiss), Portugal
- Bioinformatics, 2017. AcCNET (Accessory Genome Constellation Network): comparative genomics software for accessory genome analysis using bipartite networks
- Frontiers in Microbiology, 2017. Transfer and Persistence of a Multi-Drug Resistance Plasmid in situ of the Infant Gut Microbiota in the Absence of Antibiotic Treatment
- Royal Society of Open Science, 2017. Modelling the impact of curtailing antibiotic usage in food animals on antibiotic resistance in humans
- Annals of the New York Academy of Sciences, 2016. Genomic and metagenomic technologies to explore the antibiotic resistance mobilome