Selection and Transmission of Antimicrobial Resistance in Complex Systems

The emergence of antibiotic resistance is increasingly limiting treatment of bacterial infections. Bacteria can become resistant via a process called “horizontal gene transfer (HGT)” which enable bacteria to exchange DNA that may include resistance genes. 

Aim

This project studies the ways in which resistant bacteria can evolve in complex ecosystems, in which they can acquire genetic material that codes for antibiotic resistance.

Approach/working method

A number of techniques have been developed that can be used to characterize the reservoir of resistant bacteria in microbial ecosystems. In addition, research is being conducted into the transfer of resistant bacteria between animals and humans, including investigating whether resistant bacteria can be transferred from dogs to their owners.

(Expected) results

In the STARCS project there have been novel tools developed to identify HGT in complex ecosystems, such as the human gut. Studies conducted in experimental animal models, the community, livestock and hospitals revealed that resistance plasmids can transfer and persist even in the absence of antibiotic selection and indicated limited contribution of livestock to infections in humans. Mathematical models showed that curtailing antibiotics in livestock may have limited impact on antibiotic resistance in humans and identified the important role of the environment in antibiotic resistance transmission between livestock and human reservoir as it will mitigate (partially) the effects of livestock antibiotic curtailments.

Products

Title: Transfer and Persistence of a Multi-Drug Resistance Plasmid in situ of the Infant Gut Microbiota in the Absence of Antibiotic Treatment
Author: Heidi Gumpert 1 2 , Jessica Z Kubicek-Sutherland 3 , Andreas Porse 4 , Nahid Karami 5 , Christian Munck 4 , Marius Linkevicius 3 , Ingegerd Adlerberth 5 , Agnes E Wold 5 , Dan I Andersson 3 , Morten O A Sommer 4
Magazine: Frontiers in Microbiology, section Infectious Diseases
Title: Genomic rearrangements uncovered by genome-wide co-evolution analysis of a major nosocomial pathogen, Enterococcus faecium
Author: Janetta Top 1 , Sergio Arredondo-Alonso 1 , Anita C Schürch 1 , Santeri Puranen 2 3 , Maiju Pesonen 2 4 3 , Johan Pensar 5 2 , Rob J L Willems 1 , Jukka Corander
Magazine: BMC Genomics
Title: AcCNET (Accessory Genome Constellation Network): comparative genomics software for accessory genome analysis using bipartite networks
Author: Val F Lanza 1 2 3 , Fernando Baquero 1 2 3 , Fernando de la Cruz 4 , Teresa M Coque
Magazine: Bioinformatics
Title: Modelling the impact of curtailing antibiotic usage in food animals on antibiotic resistance in humans
Author: B A D van Bunnik 1 , M E J Woolhouse
Magazine: The Royal Society Open Access
Title: Quantifying the transmission of antimicrobial resistance at the human and livestock interface with genomics
Author: Bryan A Wee 1 , Dishon M Muloi 2 , Bram A D van Bunnik
Magazine: Clinical Microbiology and Infection
Title: A cross-sectional survey of practices and knowledge among antibiotic retailers in Nairobi, Kenya
Author: Dishon Muloi 1 2 3 4 , Eric M Fèvre 5 3 4 , Judy Bettridge 5 3 , Robert Rono 3 , Daniel Ong'are 3 , James M Hassell 5 3 , Maurice K Karani 3 , Patrick Muinde 3 , Bram van Bunnik 1 2 , Alice Street 6 , Margo Chase-Topping 2 7 , Amy B Pedersen 8 , Melissa J Ward 2 9 , Mark Woolhouse
Magazine: Globalisation and Health
Title: Prospective One Health genetic surveillance in Vietnam identifies distinct bla CTX-M-harbouring Escherichia coli in food-chain and human-derived samples
Author: Minh Ngoc Nguyen 1 , Ha Thi Thu Hoang 2 , Basil Britto Xavier 1 , Christine Lammens 1 , Hai Thanh Le 3 , Ngoc Thi Bich Hoang 3 , Son Thai Nguyen 4 , Ngoc Thi Pham 5 , Herman Goossens 1 , Anh Duc Dang 3 , Surbhi Malhotra-Kumar 6
Magazine: Clinical Microbiology and Infection
Title: Are Food Animals Responsible for Transfer of Antimicrobial-Resistant Escherichia coli or Their Resistance Determinants to Human Populations? A Systematic Review
Author: Dishon Muloi 1 2 , Melissa J Ward 2 3 , Amy B Pedersen 2 , Eric M Fèvre 4 5 , Mark E J Woolhouse 1 2 , Bram A D van Bunnik
Magazine: International Journal of Food Microbiology
Title: In-depth resistome analysis by targeted metagenomics
Author: Val F Lanza 1 2 3 4 , Fernando Baquero 1 2 3 , José Luís Martínez 2 4 , Ricardo Ramos-Ruíz 5 , Bruno González-Zorn 6 , Antoine Andremont 7 , Antonio Sánchez-Valenzuela 1 , Stanislav Dusko Ehrlich 8 9 , Sean Kennedy 8 10 , Etienne Ruppé 7 8 , Willem van Schaik 11 12 , Rob J Willems 11 , Fernando de la Cruz 13 14 , Teresa M Coque 15 16 17
Magazine: Bioinformatics
Title: gplas: a comprehensive tool for plasmid analysis using short-read graphs
Author: Sergio Arredondo-Alonso 1 , Martin Bootsma 2 3 , Yaïr Hein 3 , Malbert R C Rogers 1 , Jukka Corander 4 5 6 , Rob J L Willems 1 , Anita C Schürch
Magazine: Bioinformatics
Title: Chromosome organization by a conserved condensin-ParB system in the actinobacterium Corynebacterium glutamicum
Author: Kati Böhm 1 , Giacomo Giacomelli 1 2 , Andreas Schmidt 3 , Axel Imhof 3 , Romain Koszul 4 5 , Martial Marbouty 6 , Marc Bramkamp
Magazine: Nature Communications
Title: Defining and combating antibiotic resistance from One Health and Global Health perspectives
Author: Sara Hernando-Amado 1 , Teresa M Coque 2 , Fernando Baquero 2 , José L Martínez
Magazine: Nature Microbiology
Title: Genomic and metagenomic technologies to explore the antibiotic resistance mobilome
Author: José L Martínez 1 , Teresa M Coque 2 3 4 , Val F Lanza 2 3 4 , Fernando de la Cruz 5 , Fernando Baquero
Magazine: Annals of the New York Acadamy of Sciences
Title: 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)
Author: T D Verschuuren 1 , D van Hout 1 , S Arredondo-Alonso 2 , A C Fluit 2 , E A Reuland 2 3 4 , J Top 2 , A C Schürch 2 , T Bosch 4 , M J M Bonten 1 2 , J A J W Kluytmans 1 , R J L Willems 2
Magazine: Journal of Antimicrobial Chemotherapy
Title: Prediction of the intestinal resistome by a three-dimensional structure-based method
Author: Etienne Ruppé 1 2 , Amine Ghozlane 3 4 5 , Julien Tap 3 6 , Nicolas Pons 3 , Anne-Sophie Alvarez 3 , Nicolas Maziers 3 , Trinidad Cuesta 7 , Sara Hernando-Amado 7 , Irene Clares 7 , Jose Luís Martínez 7 , Teresa M Coque 8 9 10 , Fernando Baquero 8 9 10 , Val F Lanza 8 9 , Luis Máiz 11 , Tiphaine Goulenok 12 , Victoire de Lastours 13 12 , Nawal Amor 12 , Bruno Fantin 13 12 , Ingrid Wieder 14 , Antoine Andremont 13 14 , Willem van Schaik 15 16 , M
Magazine: Nature Microbiology
Title: Potential in vivo transfer of a bla CTX-M14-harbouring plasmid established by combining long- and short-read sequencing
Author: Basil Britto Xavier 1 , Gesuele Renzi 2 , Christine Lammens 1 , Abdessalam Cherkaoui 2 , Herman Goossens 1 , Jacques Schrenzel 2 , Stephan Harbarth 3 , Surbhi Malhotra-Kumar
Magazine: Journal of Microbiology Methods
Title: Antibiotic Resistance: Moving From Individual Health Norms to Social Norms in One Health and Global Health
Author: Sara Hernando-Amado 1 , Teresa M Coque 2 , Fernando Baquero 2 , José L Martínez
Magazine: Frontiers in Microbiology, section Infectious Diseases
Title: The Origin of Niches and Species in the Bacterial World
Author: Fernando Baquero 1 , Teresa M Coque 1 , Juan Carlos Galán 1 , Jose L Martinez
Magazine: Frontiers in Microbiology, section Infectious Diseases
Title: Gene Transmission in the One Health Microbiosphere and the Channels of Antimicrobial Resistance
Author: Fernando Baquero 1 , Teresa M Coque 1 , José-Luis Martínez 2 , Sonia Aracil-Gisbert 1 , Val F Lanza
Magazine: Frontiers in Microbiology, section Infectious Diseases
Title: MetaTOR: A Computational Pipeline to Recover High-Quality Metagenomic Bins From Mammalian Gut Proximity-Ligation (meta3C) Libraries
Author: Lyam Baudry 1 2 3 , Théo Foutel-Rodier 1 2 3 , Agnès Thierry 1 2 , Romain Koszul 1 2 , Martial Marbouty
Magazine: frontiers in genetics
Title: The challenges of designing a benchmark strategy for bioinformatics pipelines in the identification of antimicrobial resistance determinants using next generation sequencing technologies
Author: Alexandre Angers-Loustau 1 , Mauro Petrillo 1 , Johan Bengtsson-Palme 2 3 , Thomas Berendonk 4 , Burton Blais 5 , Kok-Gan Chan 6 7 , Teresa M Coque 8 , Paul Hammer 9 , Stefanie Heß 4 , Dafni M Kagkli 1 , Carsten Krumbiegel 9 , Val F Lanza 8 , Jean-Yves Madec 10 , Thierry Naas 11 , Justin O'Grady 12 , Valentina Paracchini 1 , John W A Rossen 13 , Etienne Ruppé 14 , Jessica Vamathevan 15 , Vittorio Venturi 16 , Guy Van den Eede
Magazine: F1000 Research
Title: MetaHiC phage-bacteria infection network reveals active cycling phages of the healthy human gut
Author: Martial Marbouty 1 , Agnès Thierry 1 , Gaël A Millot 2 , Romain Koszul 1
Magazine: eLife
Title: Selection of Resistant Bacteria in Mallards Exposed to Subinhibitory Concentrations of Ciprofloxacin in Their Water Environment
Author: Clara Atterby 1 , Marie Nykvist 2 , Ulrika Lustig 2 , Dan I Andersson 2 , Josef D Järhult # 3 , Linus Sandegren
Magazine: Antimicrobial Agents and Chemotherapy
Title: Plasmids Shaped the Recent Emergence of the Major Nosocomial Pathogen Enterococcus faecium
Author: S Arredondo-Alonso # 1 , J Top # 1 , A McNally 2 , S Puranen 3 4 , M Pesonen 3 4 , J Pensar 4 , P Marttinen 4 , J C Braat 1 , M R C Rogers 1 , W van Schaik 2 , S Kaski 3 , R J L Willems # 5 , J Corander # 6 7 8 , A C Schürch
Magazine: mBio
Title: The global dissemination of hospital clones of Enterococcus faecium
Author: Sebastiaan J van Hal 1 2 , Rob J L Willems 3 , Theodore Gouliouris 4 , Susan A Ballard 5 , Teresa M Coque 6 7 , Anette M Hammerum 8 , Kristin Hegstad 9 10 , Hendrik T Westh 11 , Benjamin P Howden 5 , Surbhi Malhotra-Kumar 12 , Guido Werner 13 , Katsunori Yanagihara 14 , Ashlee M Earl 15 , Katherine E Raven 16 , Jukka Corander 17 18 , Rory Bowden 19 20 21 , Enterococcal Group
Magazine: Genome medicine
Title: Genome Dynamics of Escherichia coli during Antibiotic Treatment: Transfer, Loss, and Persistence of Genetic Elements In situ of the Infant Gut
Author: Andreas Porse 1 , Heidi Gumpert 2 , Jessica Z Kubicek-Sutherland 3 , Nahid Karami 4 , Ingegerd Adlerberth 4 , Agnes E Wold 4 , Dan I Andersson 3 , Morten O A Sommer
Magazine: Frontiers in Microbiology, section Infectious Diseases
Title: Mode and dynamics of vanA-type vancomycin resistance dissemination in Dutch hospitals
Author: Sergio Arredondo-Alonso 1 2 , Janetta Top 1 , Jukka Corander 2 3 4 , Rob J L Willems 1 , Anita C Schürch
Magazine: Genome medicine
Title: Apparent nosocomial adaptation of Enterococcus faecalis predates the modern hospital era
Author: Anna K Pöntinen 1 , Janetta Top 2 , Sergio Arredondo-Alonso 3 2 , Gerry Tonkin-Hill 4 , Ana R Freitas 5 , Carla Novais 5 , Rebecca A Gladstone 3 , Maiju Pesonen 6 , Rodrigo Meneses 2 , Henri Pesonen 3 , John A Lees 7 , Dorota Jamrozy 4 , Stephen D Bentley 4 , Val F Lanza 8 , Carmen Torres 9 , Luisa Peixe 5 , Teresa M Coque 10 11 , Julian Parkhill 12 13 , Anita C Schürch # 2 , Rob J L Willems # 2 , Jukka Corander
Magazine: Nature Communications
Title: 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
Author: Linus Sandegren 1 , Johan Stedt 2 , Ulrika Lustig 1 , Jonas Bonnedahl 2 3 , Dan I Andersson 1 , Josef D Järhult
Magazine: Environmental Microbiology
Title: Evolutionary Pathways and Trajectories in Antibiotic Resistance
Author: F Baquero 1 , J L Martínez 2 , V F Lanza 1 3 , J Rodríguez-Beltrán 1 , J C Galán 1 , A San Millán 2 , R Cantón 1 , T M Coque
Magazine: Clinical Microbiology reviews
Title: mlplasmids: a user-friendly tool to predict plasmid- and chromosome-derived sequences for single species
Author: Sergio Arredondo-Alonso 1 , Malbert R C Rogers 1 , Johanna C Braat 1 , Tess D Verschuuren 2 , Janetta Top 1 , Jukka Corander 3 4 5 , Rob J L Willems 1 , Anita C Schürch 1
Magazine: Microbiology
Title: Novel computational approaches to predict and reconstruct bacterial plasmids
Author: Sergio Arredondo Alonso

Reports


Endreport

Bacteriën worden in toenemende mate resistent tegen antibiotica. Dit is een directe bedreiging voor de gezondheidszorg in Nederland en daarbuiten. Recente studies tonen aan dat in Europa meer dan 30.000 mensen per jaar overlijden ten gevolge van een infectie met een antibioticum-resistente bacterie. Dit project bestudeert de manieren waarbij resistente bacteriën kunnen evolueren in complexe ecosystemen, waarin zij genetisch materiaal kunnen verwerven dat codeert voor antibioticum resistentie. Hiervoor zijn een aantal technieken ontwikkeld die kunnen worden gebruikt om het reservoir van resistente bacteriën te karakteriseren in microbiële ecosystemen. Bovendien vindt onderzoek plaats naar de overdracht van resistente bacteriën tussen dier en mens, waarbij we onder meer onderzoeken of resistente bacteriën overgedragen kunnen worden van honden naar hun eigenaars.
Bacteriën worden in toenemende mate resistent tegen antibiotica. Dit is een directe bedreiging voor de gezondheidszorg in Nederland en daarbuiten. Recente studies tonen aan dat in Europa meer dan 30.000 mensen per jaar overlijden ten gevolge van een infectie met een antibioticum-resistente bacterie. Dit project bestudeert de manieren waarbij resistente bacteriën kunnen evolueren in complexe ecosystemen, waarin zij genetisch materiaal kunnen verwerven dat codeert voor antibioticum resistentie. Hiervoor zijn een aantal technieken ontwikkeld die kunnen worden gebruikt om het reservoir van resistente bacteriën te karakteriseren in microbiële ecosystemen. Bovendien vindt onderzoek plaats naar de overdracht van resistente bacteriën tussen dier en mens, waarbij we onder meer onderzoeken of resistente bacteriën overgedragen kunnen worden van honden naar hun eigenaars.

Subjects

Features

Project number:
547001009
Duration: 100%
Duration: 100 %
2017
2021
Part of programme:
Related funding round:
Project lead and secretary:
Dr. R.J.L. Willems
Responsible organisation:
Universitair Medisch Centrum Utrecht