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Microbiome Invasion and Transmission ofplasmid-mediated Antimicrobial Resistance (MITAR)

Projectomschrijving

Bacteriën kunnen resistentie tegen antibiotica overdragen door middel van plasmiden, kleine circulaire DNA-moleculen. Deze plasmide-overgedragen resistentie komt voor bij mensen, dieren en in het milieu. Steeds nieuwe varianten komen op en het is niet goed bekend welke eigenschappen zorgen voor de verspreiding van plasmide-overgedragen resistentie in een microbiologisch ecosysteem zoals dat in de darm.
Dit project zal door middel van laboratorium experimenten en wiskundige modellen onderzoeken welke eigenschappen van de resistentie én van de darmflora van belang zijn voor de verspreiding tussen kippen. Ook de evolutie van de betrokken bacteriën en plasmiden zal worden bestudeerd om te zien of dit van invloed is op de verspreiding tussen dieren.
Dit project zal bijdragen aan een beter begrip van deze vormen van antibioticum resistentie en modellen ontwikkelen om beheersmaatregelen te evalueren en risicoanalyses uit te voeren voor nog niet ontdekte antibioticum resistenties.

Producten

Titel: Data from: Chicken gut microbiome members limit the spread of an antimicrobial resistance plasmid in Escherichia coli
Auteur: Duxbury, Sarah, Alderliesten, Jesse, Zwart, Mark, Stegeman, Arjan, Fischer, Egil, de Visser, Arjan
Titel: The ecology and evolution of plasmid-mediated antimicrobial resistance (pAMR) transfer
Auteur: Sarah Duxbury, Mark Zwart, Jesse Alderliesten, Egil Fischer, Arjan Stegeman, Dik Mevius and Arjan de Visser
Link: http://nlseb.nl/meetings/meeting-2018/
Titel: The ecology and evolution of plasmid-mediated antimicrobial resistance (pAMR) transfer in the microbiome
Auteur: Sarah Duxbury, Mark Zwart, Jesse Alderliesten, Egil Fischer, Arjan Stegeman, Dik Mevius and Arjan de Visser
Link: https://eseb.org/wp-content/uploads/2019/09/ESEB2019_Program.pdf
Titel: Ecology and evolution of plasmid-mediated antimicrobial resistance spread in the chicken gut microbiome
Auteur: Sarah Duxbury, J.B. Alderliesten, M.P. Zwart, A. Stegeman, E.A.J. Fischer, J.A.G.M. de Visser
Link: http://nlseb.nl/nlseb2021-nlseb-phd-postdoc-meeting/
Titel: Evolutionary drivers of plasmid mediated antimicrobial resistance pAMR): from the field to the laboratory and back
Auteur: Sarah Duxbury Egil A.J. Fischer Jesse Alderliesten Mark Zwart Arjan Stegeman Arjan de Visser
Titel: The ecology and evolution of plasmid-mediated antimicrobial resistance (pAMR) transfer in the microbiome
Auteur: Sarah Duxbury, Mark Zwart, Jesse Alderliesten, Egil Fischer, Arjan Stegeman, Dik Mevius and Arjan de Visser
Link: https://eseb.org/wp-content/uploads/2018/08/2018_Program.pdf
Titel: The ecology and evolution of plasmid-mediated antimicrobial resistance (pAMR) transfer in the microbiome
Auteur: Sarah Duxbury
Titel: Plasmid transfer is more efficient between phylogenetically closer related bacteria: a literature review
Auteur: Alderliesten, J.B. Fischer, E.A.J. Duxbury, S. De Visser, A. Zwart, M. Stegeman, J.A.
Link: http://www.veterinaryscienceday.nl
Titel: Ecology and evolution of plasmid-mediated antimicrobial resistance transfer in the chicken gut microbiome
Auteur: Sarah Duxbury, J.B. Alderliesten, M.P. Zwart, A. Stegeman, E.A.J. Fischer, J.A.G.M. de Visser
Link: http://www.knvm.org/events/6457-calendar/annual-fall-knvm-microbial-ecology-symposium
Titel: Plasmid transfer is more efficient between phylogenetically closer related bacteria: a literature review
Auteur: Alderliesten, J.B. Fischer, E.A.J. Duxbury, S. De Visser, A. Zwart, M. Stegeman, J.A.
Titel: The ecology and evolution of plasmid-mediated antimicrobial resistance (pAMR) transfer in the microbiome
Auteur: Sarah Duxbury, Mark Zwart, Jesse Alderliesten, Egil Fischer, Arjan Stegeman, Dik Mevius and Arjan de Visser
Link: http://nlseb.nl/meeting-2019/
Titel: Microbiome Invasion and Transmission of plasmid-mediated Antimicrobial Resistance (MITAR)
Auteur: Egil A.J. Fischer Sarah Duxbury Jesse Alderliesten
Link: https://mitar.sites.uu.nl/
Titel: Effect of donor-recipient relatedness on the plasmid conjugation frequency: a meta-analysis
Auteur: Jesse B. Alderliesten, Sarah J. N. Duxbury, Mark P. Zwart, J. Arjan G. M. de Visser, Arjan Stegeman & Egil A. J. Fischer
Magazine: BMC Microbiology
Titel: Second compartment widens plasmid invasion conditions: two-compartment pair-formation model of conjugation in the gut
Auteur: Jesse B.Alderliesten Mark P.Zwart J. Arjan G.M.de Visser Arjan Stegeman Egil A.J.Fischer
Magazine: Journal of Theoretical Biology
Link: https://doi.org/10.1016/j.jtbi.2021.110937
Titel: Estimating the rate of plasmid transfer in liquid mating cultures
Auteur: Jana S. Huisman,Fabienne Benz, Sarah J.N. Duxbury, J. Arjan G.M. de Visser,Alex R. Hall, Egil A.J. Fischer, Sebastian Bonhoeffer
Magazine: BioRxiv
Link: https://www.biorxiv.org/content/10.1101/2020.03.09.980862v1.full
Titel: Data from: Chicken gut microbiome members limit the spread of an antimicrobial resistance plasmid in Escherichia coli
Auteur: Duxbury, Sarah, Alderliesten, Jesse, Zwart, Mark, Stegeman, Arjan, Fischer, Egil, De Visser, Arjan

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Samenvatting van de aanvraag

Plasmid-mediated antimicrobial resistance (pAMR) occurs in both humans and animals and requires One-health solutions, which include a holistic approach integrating veterinary, medical and environmental disciplines. Reduction of antimicrobial usage is one of the measures against further proliferation of pAMR. The prevalence of pAMR in poultry remains, however, high after reductions in antimicrobial usage, and new forms of pAMR arise (e.g. mcr-1). In humans, a parallel problem occurs rendering pathogens multi-resistant. Currently we are not able to assess the risk of new pAMR to invade the microbiome of an individual (human or animal) and whether it can be maintained within the microbiomes of a population of individuals. Understanding the key features of the microbiome determining the potential for invasion, colonization and evolution of pAMR is essential to lower the barriers for new innovative interventions. This project will provide both mathematical models and experimental set-ups to assess the ecological and evolutionary dynamics of pAMR in the microbiomes of groups of chickens. We will develop mathematical models for within-animal and between-animal dynamics of pAMR. The mathematical models will be structured so that they can be generalized to humans and other livestock species in the future. The following research questions will be investigated: Which microbial community properties makes pAMR prolific? Can the resident microbial community prevent invasion of plasmid-mediated antibiotic resistance, or does the resident community facilitate invasion? Does the microbiome effect host-plasmid coevolution, and can there still be rapid coevolution and improvements in the competitive ability of host-plasmid combinations in the presence of the microbiome? Considering the transmission bottleneck, are plasmids more likely to occur in bacterial strains that excel at within-animal competition at the expense of between-animal transmission, or do they occur more often in microbial strains that are easily transmitted between animals? Is selection “short-sighted”, and does it optimize a microbe-plasmid combination for within-animal competition? For this project, a PhD student researcher will be recruited to develop a mathematical model for within- and between chicken dynamics of pAMR. Dynamical mathematical models are essential to grasp the complex interactions between pAMR and the microbiome. These models enable in silico experimentation with external perturbations, which might have all but intuitive outcomes. The dynamical mathematical models will be developed by extending the generalized Lotka-Volterra model to include plasmid dynamics of pAMR and adaptive mutations of the bacterium and the plasmid. The dynamical mathematical model will be validated and calibrated on dedicated in vivo transmission experiments of pAMR. A post-doctoral researcher will set up specifically designed in vitro experiments for parameter estimation and in vitro microbial communities to validate the within-animal model. The in vitro experiments are a flexible and relatively cheap method to study invasion and evolution of pAMR, providing crucial information on the within-host dynamics of pAMR. The in vivo experiments will show the generalizability to real-life conditions of between-host dynamics. We choose chicken as a model species, because it allows us to build on experience of previous work and to use existing data. Two currently running projects in poultry will allow for a first parameterization of the mathematical models. We will make ample use of the extensive data sets collected within these projects on the chicken microbiome and transmission of ESBLs between chickens, as well as the previous ZonMW-financed PEDEP study. Additionally, pAMR in poultry is highly relevant, because pAMR has a high prevalence in chicken production systems. The MITAR project proposed here will strengthen our understanding of the ecological and evolutionary dynamics by extensive dynamical mathematical modelling. The MITAR project will provide mathematical, in vitro and in vivo models to assess the risk of new pAMR, which will be highly useful for the development of interventions and policy measures on pAMR. The mathematical models will be implemented as an open-source, publicly accessible package. Dissemination of knowledge will occur via the regular scientific channels (e.g. conferences, publications and a PhD-thesis), and through targeted workshops and a final seminar.

Onderwerpen

Kenmerken

Projectnummer:
541001005
Looptijd: 100%
Looptijd: 100 %
2017
2023
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
dr. ir. E.A.J. Fischer
Verantwoordelijke organisatie:
Universiteit Utrecht