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Microbial Genomics & Microbiomics

The Microbial Genomic & Microbiomics research group - under leadership of prof. dr. Rob Willems (who succeeded prof. dr. Marc Bonten as group leader as of 2017) - has three major research lines: (1) Molecular & Cellular Host-Microbiota Interactions, (2) Microbiomics and (3) Genomics & Genome-based Epidemiology of Antimicrobial Resistance. 

Research interests/topics

Molecular & Cellular Host-Microbiota Interactions

PI: Dr. Marcel de Zoete, associate professor

The intestinal microbiota plays a key role in health and disease, often through direct bacterial interactions with the host intestinal (immune) cells or by released bacterial metabolites. Our main goal is to understand molecular mechanisms that underly pathogenic host-microbiota interactions. An important focus are ‘pathogenic’ commensals called pathobionts, which often live within the intestinal mucus layer in close proximity or attached to intestinal epithelial cells. The interactions of these pathobionts with the host epithelium and immune system are mostly unclear but believed to dramatically impact on various disease, including inflammatory bowel disease, colorectal cancer and metabolic syndrome. By unraveling the molecular mechanisms behind pathological host-microbiota interactions, we aim to pave the road for the development of novel therapeutic approaches.

More about Molecular & Cellular Host-Microbiota Interactions

Microbiomics

PI: Dr. Fernanda Paganelli, assistant professor

We use next generation sequencing techniques to determine the role of the microbiome in relation to disease, such as chronic infectious and immunological diseases as well as transmission of antibiotic resistant genes in communities and hospitals. Furthermore, we use colon organoids model to study the host response to specific bacterial communities.

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Genomics & Genome-based Epidemiology of Antimicrobial Resistance

PI: Dr. Anita Schürch, assistant professor

Dissemination of physiologically important traits encoded on plasmids, integrons, transposons, and bacteriophages are highly dynamic because these mobile genetic elements (MGE) transmit with ease. The most prominent example is the spread of antimicrobial resistance (AMR) genes through different hosts and environments. We develop novel computational methods to reconstruct plasmids and other MGEs and to map their dissemination. Several genomics software tools have been developed and made made publicly available by this research group, including Gplas and mlplasmids.

More about Genomics & Genome-based Epidemiology of Antimicrobial Resistance

About the group leader(s) uitklapper, klik om te openen

Prof. dr. Rob Willems studied biology at the Free University in Amsterdam and acquired his PhD from the Utrecht University in 1993 on “Genetic and functional studies on Bordetella pertussis fimbriae”. After postdoc positions at the Faculty of Veterinary Medicine, Utrecht University and at the Department of Infectious Diseases of the University Hospital, Leiden he became research scientist and section head at the National Institute for Public Health and the Environment (RIVM) in 1996. In 2003 he moved from the RIVM to the University Medical Center Utrecht where he became assistant professor. In 2008 he was appointed associate professor and since December 1st 2016, he is full professor of Population Genetics of Antibiotic Resistance at the department of Medical Microbiology of the University Medical Center Utrecht.

Group members uitklapper, klik om te openen

Assistant professor:
Dr. Janetta Top

Postdocs:
Dr. Victoria Pascal

PhD candidates and their research projects:
Guus van Muijlwijk
Jiannan Cui
Coco Duizer
Jesse Kerkvliet - "Gene flow networks in animals, the food chain and the environment"
Paul Stege - "Molecular mechanisms of microbiota-mediated colonization resistance against intestinal outgrowth of multidrug-resistant Enterobacteriaceae (E. coli, K. pneumoniae) and enterococci"
Roos Berbers
Jery Baan
Julian Paganini - "Population genomics of antibiotic-resistant E. coli and potential plasmid transmission in ICU patients"
Matteo Buffoni - "Mobile Genetic Elements involved in Antimicrobial Resistance"
Rick Verheijden

Bioinformaticians:
Malbert Rogers
Rodrigo Silva Meneses

Research technicians:
Marco Viveen
Iris Braat
Jelle Scharringa
Moniek Salomons

Key publications uitklapper, klik om te openen

Top J, Hendrickx APA, van Ampting MTJ, van Limpt K, Knol J, van de Kamer D, Braat JC, Viveen M, Rogers MR, Kemperman H, Willems RJL, Paganelli FL. 
Low-calcium diet in mice leads to reduced gut colonization by Enterococcus faecium.
Microbiology Open 2019;8(12):e936.

Ten Doesschate T, Abbott IJ, Willems RJL, Top J, Rogers MRC, Bonten MM, Paganelli FL. 
In vivo acquisition of fosfomycin resistance in Escherichia coli by fosA transmission from commensal flora.
Journal of Antimicrobial Chemotherapy 2019;74(12):3630–3632

Paganelli FL, Luyer M, Hazelbag CM, Uh HW, Rogers MRC, Adriaans D, Berbers RM, Hendrickx APA, Viveen MC, Groot JA, Bonten MJM, Fluit AC, Willems RJL, Leavis HL. 
Roux-Y Gastric Bypass and Sleeve Gastrectomy directly change gut microbiota composition independent of surgery type.
Sci Rep 2019;9(1):10979

Schurch AC, Arredondo-Alonso S, Willems RJL, Goering RV.
Whole genome sequencing options for bacterial strain typing and epidemiological analysis based on single nucleotide polymorphism vs gene-by-gene-based approaches.
Clin Microbiol Infect 2018;24(4):350-4

Arredondo-Alonso S, Rogers MRC, Braat JC, Verschuuren TD, Top J, Corander J, Willems RJL, Schurch AC.
mlplasmids: a user-friendly tool to predict plasmid- and chromosome-derived sequences for single species. 
Microbial Genomics 2018;4(11):224

Paganelli FL, Leavis HL, He S, van Sorge NM, Payré C, Lambeau G, Willems RJL, Rooijakkers SHM.
Group IIA-Secreted Phospholipase A2 in Human Serum Kills Commensal but Not Clinical Enterococcus faecium Isolates. 
Infect  Immun 2018;86(8):e00180-18.

Arredondo-Alonso S, Willems RJ, van Schaik W, Schurch AC. 
On the (im) possibility of reconstructing plasmids from whole-genome short-read sequencing data.
Microbial Genomics 2017;3(10):e000128

Schurch AC, van Schaik W.
Challenges and opportunities for whole-genome sequencing–based surveillance of antibiotic resistance.
Ann New York Acad Sci 2017;1388(1):108–120

Education / Courses uitklapper, klik om te openen

Achievements uitklapper, klik om te openen

Funding & Grants

2020 - ZonMw-ABR - €250.000
“VRE-Crosswords, horizontal or vertical? Transmission of vancomycin-resistant Enterococcus faecium in Dutch hospitals (Applicant: dr. Anita Schürch)

2020 - Health~Holland - €1.000.000
DiSSeMINATE - Drivers of Selection and Spread of Mobile Genetic Elements Involved in antimicrobial resistance (Applicant: dr. Anita Schürch).

2019 - Netherlands Center for One Health (NCOH) - €250.000
NCOH PhD programme ‘Complex Systems’ - Gene flow networks in animals, the food chain and the environment (Applicants: prof. dr. Rob Willems & dr. Anita Schürch).

2019 - Janssen - €207.000
VAC52416BAC0008

2019 - Janssen - €250.000
VAC52416BAC0001

2018 - Janssen - €1.028.000
63871860BAC0006

2018 - University of Helsinki - €90.000

2018 - One Health EJP - €39.000
MedVetKlebs JRP: Klebsiella pneumoniae: from ecology to source attribution and transmission control

2017 - Netherlands Centre for One Health - €250.000
Metagenomics: Molecular mechanisms of microbiota-mediated colonization resistance against intestinal outgrowth of multidrug-resistant Enterobacteriaceae (E. coli, K. pneumoniae) and enterococci

2016 - Horizon 2020 - JPI-EC-AMR JTC - €1,919.000
Selection and Transmission of Antimicrobial Resistance in Complex Systems (STARCS)

2015 - Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) - €800.000
Vidi grant for dr. Marcel de Zoete

2014 - University of Helsinki - €225.000
Whole genome sequencing of Enterococcus faecium

Alumni / PhD theses uitklapper, klik om te openen

Mechanisms and evolution of colistin resistance in gram-negative bacteria
Dr. Axel Janssen
2020
Axel Janssen (1991, Nijmegen) defended his PhD thesis on November 4, 2020 at Utrecht University. The title of his thesis was “Mechanisms and evolution of colistin resistance in clinical Enterobacteriaceae”. Supervisors were prof. dr. Rob Willems and prof. dr. ir. Willem van Schaik (Department of Medical Microbiology, UMC Utrecht).

Novel computational approaches to predict and reconstruct bacterial plasmids
Dr. Sergio Arredondo Alonso
2020
Sergio Arredondo Alonso (1993, Barcelona) received his PhD on September 21, 2020 at Utrecht University. The title of his thesis was “Novel computational approaches to predict and reconstruct bacterial plasmids”. Supervisor was prof. dr. Rob Willems and co-supervisor was dr. Anita Schürch (both Department of Medical Microbiology, UMC Utrecht).

Elucidating the success of Enterococcus faecium as a nosocomial pathogen through functional genomics
Ana Maria Guzmann Prieto
2017
Ana Maria Guzman Prieto (1982, Santiago de Cali, Colombia) received her PhD on May 23, 2017 at Utrecht University. The title of her thesis was “Elucidating the success of Enterococcus faecium as a nosocomial pathogen through functional genomics”. Supervisors were prof. dr. Rob Willems, prof. dr. Marc Bonten and prof. dr. Willem van Schaijk (all Department of Medical Microbiology, UMC Utrecht).

The human gut microbiota as a reservoir for antimicrobial resistance genes
Elena Buelow
2015
Elena Buelow (1982, Kevelaer, Germany) received her PhD on March 24, 2015 at Utrecht University. The title of her thesis was “The human gut microbiota as a reservoir for antimicrobial resistance genes”. Supervisor was prof. dr. Marc Bonten snd co-supervisors were prof. dr. Rob Willems and prof. dr. Willem van Schaijk (all Department of Medical Microbiology, UMC Utrecht).

Biogenesis of Enterococcis faecium biofilms
Fernanda Paganelli
2015
Fernanda Paganelli (1985, Sao Paulo, Brazil) received her PhD on February 26, 2015 at Utrecht University. The title of her thesis was “Biogenesis of Enterococcis faecium biofilms”. Supervisor was prof. dr. Marc Bonten and co-supervisors were dr. Helen Leavis and dr. Rob Willems (all Department of Medical Microbiology, UMC Utrecht).

Pseudomonas aeruginosa colonization in patients with cystic fibrosis; population structure, the Dutch clone and effects of segregation
Rosa van Mansfeld
2014
Rosa van Mansfeld (1978, Woerden) received her PhD on November 27, 2014 at Utrecht University. The title of her thesis was “Pseudomonas aeruginosa colonization in patients with cystic fibrosis; population structure, the Dutch clone and effects of segregation”. Supervisors were prof. dr. Marc Bonten (Department of Medical Microbiology, UMC Utrecht) and prof. dr. Kors van der Ent (Department of Pulmonary Diseases, Wilhelmins Children's Hospital) and co-supervisor was dr. Rob Willems (Department of Medical Microbiology, UMC Utrecht).

Functional genomics of Enterococcus faecium: antibiotic resistance and niche adaptation
Xinlin Zhang
2013
Xinglin Zhang (1982, Linyi, China) received his PhD on April 12, 2013 at Utrecht University. The title of his thesis was “Functional genomics of Enterococcus faecium: antibiotic resistance and niche adaptation”. Supervisor was prof. dr. Marc Bonten and co-supervisors were dr. Rob Willems, dr. ir. Willem van Schaijk (all Department of Medical Microbiology, UMC Utrecht).

A genomic approach to explore the development and evolution of methicillin-resistant staphylococci
Neeltje Carpaij
2011
Neeltje Carpaij (1981, Eindhoven) received her PhD on November 22, 2011 at Utrecht University. The title of his thesis was “A genomic approach to explore the development and evolution of methicillin-resistant staphylococci”. Supervisor was prof. dr. Marc Bonten and co-supervisors were dr. Rob Willems and dr. Ad Fluit (all Department of Medical Microbiology, UMC Utrecht).

Ampicillin-resistant Enterococcus faecium ecology, transmission and intervention strategies
Marieke de Regt
2010
Marieke de Regt (1981, Terheijden) received her PhD on December 16, 2010 at Utrecht University. The title of her thesis was “Ampicillin-resistant Enterococcus faecium ecology, transmission and intervention strategies”. Supervisor was prof. dr. Marc Bonten and co-supervisor was dr. Rob Willems (both Department of Medical Microbiology, UMC Utrecht).

The role of Enterococcal Surface Protein in the pathogenesis of Enterococcus faecium infections
Esther Heikens
2009
Esther Heikens (1976, Zwolle) received her PhD on December 1, 2009 at Utrecht University. The title of her thesis was “The role of Enterococcal Surface Protein in the pathogenesis of Enterococcus faecium infections”. Supervisor was prof. dr. Marc Bonten and co-supervisor was dr. Rob Willems (both Department of Medical Microbiology, UMC Utrecht).

Cell Wall-anchored Proteins of Enterococcus faecium: Exploring a Novel Surface
Antoni Hendrickx
2009
Antoni Hendrickx (1980, Amsterdam) received his PhD on December 1, 2009 at Utrecht University. The title of his thesis was “Cell Wall-anchored Proteins of Enterococcus faecium: Exploring a Novel Surface”. Supervisor was prof. dr. Marc Bonten and co-supervisor were dr. Rob Willems (Department of Medical Microbiology, UMC Utrecht) and dr. Willem van Wamel (Erasmus MC, Rotterdam).

Enterococcus faecium infections : where bacterial virulence meets innate immunity
Masja Leendertse
2009
Masja Leendertse (1976, Ouder-Amstel) received her PhD on June 18, 2009 at Utrecht University. The title of her thesis was “Enterococcus faecium infections : where bacterial virulence meets innate immunity”. Supervisors were prof. dr. Marc Bonten (Department of Medical Microbiology, UMC Utrecht) and prof. dr. Ton van der Pol (University of Amsterdam) and co-supervisor was dr. Rob Willems (Department of Medical Microbiology, UMC Utrecht).

Evolutionary Insights into CC17 Enterococcus faecium
Helen Leavis
2007
Helen Leavis received her PhD on December 6, 2007 at Utrecht University. The title of her thesis was “Evolutionary Insights into CC17 Enterococcus faecium”. Supervisor was prof. dr. Marc Bonten and co-supervisor was dr. Rob Willems (both Department of Medical Microbiology, UMC Utrecht).

Molecular epidemiology of Enterococcus faecium: from commensal to hospital adapted pathogen
Janetta Top
2007
Janetta Top (1965, Woerden) received her PhD on May 10, 2007 at Utrecht University. The title of her thesis was “Molecular epidemiology of Enterococcus faecium: from commensal to hospital adapted pathogen”. Supervisor was prof. dr. Marc Bonten and co-supervisor was dr. Rob Willems (both Department of Medical Microbiology, UMC Utrecht).

Collaborations uitklapper, klik om te openen

UMC Utrecht (Netherlands)

Prof. dr. Jeffrey Beekman, Department of Pediatrics, Wilhelmina Children's Hospital

Prof. dr. Onno Kranenburg, Laboratory for Translational Oncology, dLAB

Prof. dr. Jurgen Kuball, Center for Translational Immunology, dLAB

Dr. Caroline Lindemans, Department of Pediatrics, Wilhelmina Children's Hospital

Prof. dr. Linde Meyaard, Center for Translational Immunology, dLab

Prof. dr. Bas Oldenburg, Department of Gastroenterology and Hepatology, dIGD

Prof. dr. Janneke van de Wijgert, Research Program Infectious Diseases, Julius Center

Prof. dr. Femke van Wijk, Center for Translational Immunology, dLAB

Dr. Noortje Ijssennagger, Center for Molecular Medicine, dLAB

Dr. Marjolein de Bruin-Weller, Department of Dermatology and Allergology, dIGD

Dr. Helen Leavis, Department of Rheumatology & Clinical Immunology, dIGD

Dr. Gaby Steba, Department of Reproductive Medicine and Gynaecology, dV&B

Dr. Karijn Suijkerbuijk, Department of Medical Oncology, Cancer Center

Dr. Hae-Won Uh, Department of Biostatistics and Research Support, Julius Center

Dr. Lilly Verhagen, Department of Infectious diseases and Immunology, Wilhelmina Children's Hospital

Utrecht University (Netherlands)

Prof. dr. Jos van Putten, Institute of Veterinary Sciences, Faculty of Veterinary Medicine

Dr. Aldert Zomer, PhD, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine

Dr. Bas Dutilh, Theoretical Biology & Bioinformatics, Faculty of Sciences

Dr. ing. Tom Wennekes, Department of Pharmaceutical Sciences, Faculty of Sciences

Dr. Karin Strijbis, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine

Exeter University, Exeter (Great Britain)

Dr. Stineke van Houte, Department of Biosciences

Yale University, New Haven CT (USA)

Dr. Noah Palm, Department of Immunobiology

Hasbro Children's Hospital, Providence RI (USA)

Dr. Jason Shapiro, Department of Pediatric Gastroenterology

In the media uitklapper, klik om te openen

Contact information uitklapper, klik om te openen

Prof. dr. R.J.L. (Rob) Willems
Department of Medical Microbiology
G04.609
UMC Utrecht
The Netherlands

r.willems@umcutrecht.nl

+31 (0)88-7569185

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