Antibiotic-resistant bacteria are not new, but in the last two to three decades antibiotic resistant bacteria have been constantly increasing and rapidly spreading. As a result, the emergence of antibiotic resistance is increasingly limiting treatment options for mild to moderate infections, which makes it of pivotal importance to control the emergence and spread of antibiotic resistant nacterial pathogens.
Completed project
In the STARCS project we study the pathways by which resistant bacteria, particularly enterococci resistant to vancomycin and enterobacteriales resistant to extended-spectrum beta-lactamases, can emerge in complex ecosystems, such as the human intestinal tract, 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 and resistance genes in microbial ecosystems. In addition, we perform research into the transfer of resistant bacteria and resistance genes between animals and humans. As antibiotic resistance can spread via horizontal gene transfer of mobile genetic elemenst (MGE) in addition to the spread of antibiotic resistant strains, we have developed in the STARCS consortium novel tools to identify and reconstruct MGE’s based on whole genome sequence data and to characterize with great precision the MGE-bacteria interaction networks of the microbiota in the mammalian gut using an approach called metaHi-C.
Using all these tools studies comparing bacteria found in humans and farm animals in the Netherlands by analysing their DNA revealed that resistant bacteria found in humans were different from those found in farm animals. This shows that humans are rarely infected by antibiotic resistant bacteria that come directly from farm animals.
Furthermore, three primary studies conducted in a community setting and two in hospital settings, using samples collected from different sources: patients, live and slaughtered food animals, and environmental samples in the slaughterhouses, taken from developing (Vietnam) and developed countries (Italy, Germany) with different antibiotic use and antibiotic resistance backgrounds, revealed, again, limited contribution of food-animal sources, particularly chickens and pigs, to causing urinary tract infections by ESBL-resistant enterobacteriaceae (ESBL-E) in Hanoi, Vietnam.
In hospital settings, actively screening and decolonising patients carrying ESBL-E are promising infection control strategies. Using simple mathematical models, we were able to show that the environment that is shared between farm animals and humans might be an important pathway for the transmission of antibiotic resistant bacteria as it can act as a reservoir between the two populations. Because of this, measures such as curtailing antibiotics in farm animals have much less impact on human health.
Furthermore, our modelling showed that the effect of curtailing of antibiotic resistance in farm-animals on human foodborne diseases is two-fold. By curtailing antibiotics is farm animals the proportion of human foodborne illnesses that is caused by a resistant pathogen will be decreased, but the number of food-borne illness cases is likely to increase due to this measure. However, further modelling showed that this can be mitigated by maintaining good farm bio-security (farm-to-fork and livestock health) and reducing transmission from animals to humans.
We furthermore looked at how (international) food imports affect the efficacy of antibiotic curtailment in livestock. For this we used a simple mathematical model. This shows that imports from non-domestic sources can reduce the efficacy of local livestock antibiotic curtailment.
Project partners
- 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
Project resources
Tools
- mlplasmids: Consists of binary classifiers to predict contigs either as plasmid-derived or chromosome-derived.
- gplas: A tool to bin plasmid-predicted contigs based on sequence composition, coverage and assembly graph information.
- RFPlasmid: Predicting plasmid contigs from assemblies.
- ResCap: Repository for software, raw data tables and data bases.
- PATO: A R package designed to analyze pangenomes (set of genomes) intra or inter species.
- MetaTOR: Metagenomic Tridimensional Organisation-based Reassembly – A set of scripts that streamlines the processing and binning of metagenomic metaHiC datasets.
Video
Publications
- 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
- Genome Medicine, 2021. The global dissemination of hospital clones of Enterococcus faecium
- bioRxiv, 2021. A high-throughput multiplexing and selection strategy to complete bacterial genomes
- mBio. 2020. Plasmids Shaped the Recent Emergence of the Major Nosocomial Pathogen Enterococcus faecium.
- Microb Genom. 2020. Genomic rearrangements uncovered by genome-wide co-evolution analysis of a major nosocomial pathogen, Enterococcus faecium.
- Nat Commun. 2021. Apparent nosocomial adaptation of Enterococcus faecalis predates the modern hospital era.
- J Antimicrob Chemother. 2021. Comparative genomics of ESBL-producing Escherichia coli (ESBL-Ec) reveals a similar distribution of the 10 most prevalent ESBL-Ec clones and ESBL genes among human community faecal and extra-intestinal infection isolates in the Netherlands (2014-17).
- Front Microbiol. 2021. The Origin of Niches and Species in the Bacterial World.
- Front Microbiol. 2019. Gene Transmission in the One Health Microbiosphere and the Channels of Antimicrobial Resistance.
- Nat Microbiol. 2019. Defining and combating antibiotic resistance from One Health and Global Health perspectives.
- Methods Mol Biol. 2020. Statistical Analysis of Accessory Genome.
- Antimicrob Agents Chemother. 2021. Selection of Resistant Bacteria in Mallards Exposed to Subinhibitory Concentrations of Ciprofloxacin in Their Water Environment.
- Microbiol Resour Announc. 2021. Closed and High-Quality Bacterial Genome Sequences of the Oligo-Mouse-Microbiota Community.
- Elife. 2021. MetaHiC phage-bacteria infection network reveals active cycling phages of the healthy human gut.
- Nat Commun. 2020. Chromosome organization by a conserved condensin-ParB system in the actinobacterium Corynebacterium glutamicum.
- Front Genet. 2019. A Computational Pipeline to Recover High-Quality Metagenomic Bins From Mammalian Gut Proximity-Ligation (meta3C) Libraries.
- J Glob Health. 2019. A cross-sectional survey of practices and knowledge among antibiotic retailers in Nairobi, Kenya.
- Int J Antimicrob Agents. 2019. Epidemiology of antimicrobial-resistant Escherichia coli carriage in sympatric humans and livestock in a rapidly urbanizing city.
- Clin Microbiol Infect. 2020. Quantifying the transmission of antimicrobial resistance at the human and livestock interface with genomics.
- J Microbiol Methods. 2019. Potential in vivo transfer of a blaCTX-M14-harbouring plasmid established by combining long- and short-read sequencing.
- Clinical Microbiology Reviews, 2021. Evolutionary Pathways and Trajectories in Antibiotic Resistance (in collaboration with project ST131TS)
