Sub theme 4.4
Infections due to bacteria, fungi and parasites: diagnosis, molecular mechanisms, epidemiology, therapy and prevention


Goals of research: general outline
Scientific achievements
Future plans: special goals and approach
Running projects
Associated staff

Workgroup leaders   Department
Dr.  H. Ph.  Endtz   Medical Microbiology & Infectious Disease

Goals of research: general outline

Main focus of our recent research has been the investigation into the basic aspects of human nasal carriage of the opportunistic pathogen Staphylococcus aureus. We have defined human S. aureus nasal carriage patterns in microbiological detail. Via culture-based surveillance we can reliably discriminate between persistent and non-carriers and we have identified a number of human phenotypes that are important in establishing long-lasting colonization. These include blood glucose levels, smoking habits, gender and a variety of other parameters. In addition, we identified the first human genetic polymorphisms associated with persistent staphylococcal carriage. This emphasises the importance of host involvement in the colonization process. Recently, we have genetically solved the population structure of S. aureus strains derived from a non-clinical origin. We provided evidence that essentially any S. aureus genotype carried by humans can transform into a life-threatening pathogen but that certain clones may be even more virulent than others. In addition, in several translational studies we defined the clinical significance of genomic variability of S. aureus and validated several S. aureus molecular typing methods. Simultaneously, molecular diagnostic methods were developed and implemented. Using both the epidemiological and diagnostic methodologies we have been able to identify molecular markers important in S. aureus host specificity. Finally, we have demonstrated that host bacterium interplay is highly specific: hosts have a very clear preference for their “own” strain rather than alien isolates. While performing these studies we initiated the development of a unique human nasal colonization model.

In addition, the applicant is involved in various other translational and fundamental research projects. The development of innovative microbiological diagnostics and epidemiological typing strategies has been a continuous and scientifically productive effort over the past fifteen years. Current diagnostic and epidemiological foci involve the use of Raman and mass spectroscopy and the application of electronic nose devices. Animal models for the assessment of the therapeutic efficacy of novel antimicrobial agents and therapies have been developed and are used for identification of novel anti-infective, curative procedures.

In addition, basic research in the field of Campylobacter jejuni-induced neuropathogenesis has led to the identification of several bacterial markers for disease progression. The discovery of the involvement of the bacterial lipooligosaccharides (LOS) and its encoding genes has been the most important highlight of our studies. Some of these factors are currently being translated into innovative therapeutic approaches.

The etiology of mycetoma caused by the fungus Madurella mycetomatis has been explored as part of our collaborations with researchers from developing countries. We have developed diagnostic and typing tools, elucidated immunological response patterns in infected individuals and described the ecological spread of the fungus. In addition we unravelled some of the basic human genetic polymorphisms that predispose to the development of this devastating disease.


Scientific achievements
  1. Established human nasal colonization model for S. aureus.
  2. Solved population structure of S. aureus from non-clinical sources.
  3. Initiated genome wide association studies relating to S. aureus nasal carriage.
  4. Developed Raman spectroscopy for epidemiological typing of bacterial pathogens.
  5. Developed electronic nose device for direct microbial diagnostics.
  6. Identified C. jejuni LOS as THE molecular determinant for Guillain-Barré Syndrome.
  7. Identified human genomic markers for Madurella mycetomatis infection susceptibility.

Future plans: special goals and approach
  1. We intend to further refine our human colonization model for S. aureus.
  2. We will acquire genomics and transcriptomics technology to study S. aureus gene expression in vivo, ex vivo and in vitro.
  3. We will finalise GWA studies in collaboration with two international cohorts in which S. aureus carriage is also assessed.
  4. We will develop novel diagnostic assays based on Raman, electronic nose and MS technology, both for bacterial detection and identification as well as for antimicrobial susceptibility testing.
  5. We will further elaborate on novel C. jejuni markers for GBS; candidates are the CRISPR locus and the CRISPR associates cas genes.
  6. We will develop a prospective cohort study in Sudan in order to analyse the etiology, diagnostics, therapy and molecular basis of Madurella mycetomatis associated mycetoma.

Most recent publications
  1. Daubersies Pierre, Thomas Alan, Millet Pascal, Brahimi Karima, Langermans Jan, Ollomo Benjamin, Ben Mohamed Lbachir, Slierendregt Bas, Eling Wijnand, Belkum Alex van, Meis Jacques, Guerin-Marchand Claudine, Cayphas Sylvie, Cohen Joe, Gras-Masse Helene and Druilhe Pierre (2000) Protection against Plasmodium falciparum malaria in chimpanzees by immunization with the conserved pre-erythrocytic liver-stage 3 antigen. Nature Medicine 6, 1258-1263. (IF 26.4)
  2. Belkum Alex van, Braak Nicole van den, Godschalk Peggy, Ang Wim, Jacobs Bart, Gilbert Michel, Wakarchuk Warren, Verbrugh Henri and Endtz Hubert (2001) “A Campylobacter jejuni gene associated with immune mediated neuropathy”. Nature Medicine, 7, 752-753. (IF 26.4)
  3. Belkum Alex van, and Verbrugh Henri (2001) “Forty years of methicillin resistant Staphylococcus aureus: MRSA is here to stay – but it can be controlled.” British Medical Journal 323, 644-645. (IF 9.7)
  4. Godschalk Peggy, Heikema Astrid, Gilbert Michel, Komagamine Tomoko, Ang Wim, Glerum Jobine, Brochu Denis, Li Jiangjun, Yuki Nobuhiro, Jacobs Bart, Belkum Alex van, Endtz Hubert (2004) “The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barre Syndrome”. Journal of Clinical Investigation 114, 1659-1665. (IF 16.9)
  5. Melles Damian, Gorkink Raymond, Boelens Helene, Snijders Susan, Peeters Justine, Moorhouse Michael, Spek Peter van der, Leeuwen Willem van, Simons Guus, Verbrugh Henri, Belkum Alex van (2004) “Natural population dynamics and expansion of pathogenic clones of Staphylococcus aureus”. Journal of Clinical Investigation 114, 1732-1740. (IF 16.9)
  6. Bogaert Debbie, Belkum Alex van, Sluijter Marcel, Luijendijk Ad, Groot Ronald de, Rumke Hans, Verbrugh Henri, Hermans Peter (2004) “Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children”. Lancet 363, 1871-1872. (IF 28.6)
  7. Wertheim Heiman, Vos Margreet, Ott Alewijn, Belkum Alex van, Voss Andreas, Kluytmans Jan, Keulen Peter van, Vandenbroucke-Grauls Christina, Meester Marlene, Verbrugh Henri (2004) “Risk and outcome of nosocomial Stapohylococcus aureus bacteremia in nasal carriers versus non-carriers”. Lancet 364, 703-705. (IF 28.6)
  8. Wertheim Heiman, Vos Greet, Leeuwen Willem van, Belkum Alex van, Verbrugh Henri, Nouwen Jan (2005) “The role of nasal carriage in Staphylococcus aureus infection. Lancet Infectious Diseases 5, 751-762. (IF 12.1)
  9. Wirth Thierry, Morelli Giovanna, Kusecek Barica, Belkum Alex van,Schee Cindy van der, Meyer Axel, Achtman Mark (2007) “The rise and spread of a new pathogen: seroresistant Moraxella catarrhalis”. Genome Research 17:1647-1656. (11.2)
  10. Wertheim Heiman, Walsh Evelyn, Choudhurry Roos, Melles Damian, Boelens Helene, Miajlovic Hanna, Verbrugh Henri, Foster Tim, van Belkum Alex (2008) “Key role for clumping factor B in Staphylococcus aureus nasal colonization of humans”. PLoS Medicine 5:e17. (12.6)
  11. The complete genome sequence of Campylobacter jejuni strain 81116 (NCTC11828).
    Pearson BM, Gaskin DJ, Segers RP, Wells JM, Nuijten PJ, van Vliet AH. J Bacteriol. 2007 Nov;189(22):8402-3. Epub 2007 Sep 14.
  12. Iron-responsive repression of urease expression in Helicobacter hepaticus is mediated by the transcriptional regulator Fur. Belzer C, van Schendel BA, Kuipers EJ, Kusters JG, van Vliet AH. Infect Immun. 2007 Feb;75(2):745-52. Epub 2006 Nov 13.
  13. Helicobacter pylori and antimicrobial resistance: molecular mechanisms and clinical implications. Gerrits MM, van Vliet AH, Kuipers EJ, Kusters JG. Lancet Infect Dis. 2006 Nov;6(11):699-709. Review.
  14. Helicobacter pylori HopH (OipA) and bacterial pathogenicity: genetic and functional genomic analysis of hopH gene polymorphisms. Dossumbekova A, Prinz C, Mages J, Lang R, Kusters JG, Van Vliet AH, Reindl W, Backert S, Saur D, Schmid RM, Rad R. J Infect Dis. 2006 Nov 15;194(10):1346-55. Epub 2006 Oct 10.
  15. Urease induced calcium precipitation by Helicobacter species may initiate gallstone formation. Belzer C, Kusters JG, Kuipers EJ, van Vliet AH. Gut. 2006 Nov;55(11):1678-9. No abstract available.
  16. Pathogenesis of Helicobacter pylori infection. Kusters JG, van Vliet AH, Kuipers EJ. Clin Microbiol Rev. 2006 Jul;19(3):449-90. Review.

People associated with sub theme 4.4: Infections due to bacteria, fungi and parasites: diagnosis, molecular mechanisms, epidemiology, therapy and prevention
Name Position Department
M.  Amiri Other as mentioned (please specify in remarks) Epidemiology
MD, MSc  F.A.  Anfasa PhD-candidate Virology
dr.  C.W.  Ang Senior researcher not being a workgroup leader Medical Microbiology & Infectious Disease
Drs.  M.S.  Arcilla PhD-candidate Medical Microbiology & Infectious Disease
Mr.  Aslam MSc student (please specify in remarks) Medical Microbiology & Infectious Disease
Ing  P.N.  Atmodimedjo Technician Pathology
MSc  VB  Baede PhD-candidate Medical Microbiology & Infectious Disease
A.Y.  Baidjoe MSc student (please specify in remarks) Virology
I.  Bakker-Woudenberg Senior researcher not being a workgroup leader Medical Microbiology & Infectious Disease
Drs.  E.  van  Beek-Kok PhD-candidate Medical Microbiology & Infectious Disease
Prof.dr.  A.  van  Belkum Senior researcher not being a workgroup leader Medical Microbiology & Infectious Disease
MSc  S.  van den  Berg PhD-candidate Medical Microbiology & Infectious Disease
Dr.  M.P.  Bergman Postdoc/junior researcher Medical Microbiology & Infectious Disease
PhD, MD  A.K.  van der  Bij Physician (MD) Medical Microbiology & Infectious Disease
drs.  L.G.M.  Bode PhD-candidate Medical Microbiology & Infectious Disease
N.P.  Boeddha PhD-candidate Pediatrics
A.M.  Boelens Technician Medical Microbiology & Infectious Disease
PhD  H.J.  Bootsma Postdoc/junior researcher Pediatrics
drs.  C.A.N.  Broekhuizen PhD-candidate Rheumatology
A.B.  Broos MSc student (please specify in remarks) Medical Microbiology
Bsc  S.  van  Burgh MSc student (please specify in remarks) Medical Microbiology & Infectious Disease
Stared new concoct  Smooveb73  caraik69 Technician General Surgery
AJH  Cremers Other as mentioned (please specify in remarks) Medical Microbiology & Infectious Disease
drs  E  Cuperus PhD-candidate Anaesthesiology
MSc  M.D.  van  Dijk Postdoc/junior researcher Medical Microbiology & Infectious Disease
Telegram Hack Online  Tmmaverick  DouglascrUck Other as mentioned (please specify in remarks) General Surgery
M.S.K.  van  Dullemen Technician Medical Microbiology & Infectious Disease
K.  Eadie Technician Medical Microbiology & Infectious Disease
Paulpeter  Edwardordiz Technician General Surgery
Dr.  M. M.  van der  Eerden Physician (MD) Lung Diseases
Dr.  H. Ph.  Endtz Workgroup leader within the School Medical Microbiology & Infectious Disease
H.  Farida PhD-candidate Medical Microbiology & Infectious Disease
D.F.  Frentz PhD-candidate Virology
D.G.  Gasi PhD-candidate Pathology
MD  P.J.  van der   Geest Physician (MD) Internal Medicine
Dr.  P.C.R.  Godschalk PhD-candidate Medical Microbiology & Infectious Disease
Drs  DM  Goilo PhD-candidate Viroscience
E  van  Gorp Other as mentioned (please specify in remarks) Medical Microbiology & Infectious Disease
C.G.  Grosserichter-Wagener PhD-candidate Immunology
DVM  S.H  Hadziabdic Other as mentioned (please specify in remarks) Science and Technology
Dr.  S.  Hansenova Manaskova Other as mentioned (please specify in remarks) Radiotherapy
J.Ph.  Hays Senior researcher not being a workgroup leader Medical Microbiology & Infectious Disease
MSc  W.A.  van der   Heijden PhD-candidate Internal Medicine
A.  Heikema Senior researcher not being a workgroup leader Medical Microbiology & Infectious Disease
R.I.  Helou PhD-candidate Medical Microbiology & Infectious Disease
MD  W.  van  Herk-Alves PhD-candidate Pediatrics
Drs.  W.J.  den  Hollander PhD-candidate Gastro-enterology and Hepatology
M H  Ms.  Hossain MSc student (please specify in remarks) Postgraduate School
NSH  Hurif MSc student (please specify in remarks) Dermatology
Msc  H.H.M.  Jaeger PhD-candidate Experimental Internal Medicine
S.  Jahfari PhD-candidate Virology
W.E.  Kaman PhD-candidate Medical Microbiology & Infectious Disease
dr.  J.J.  Kerremans Postdoc/junior researcher Medical Microbiology
K.  Ahmad  Khan PhD-candidate Medical Microbiology & Infectious Disease
Drs.  Ahmad  Khan PhD-candidate Medical Microbiology & Infectious Disease
MSc.  W  Kloezen PhD-candidate Medical Microbiology & Infectious Disease
MSc  V.A.C.M.  Koeken PhD-candidate Internal Medicine
arts-onderzoeker  J.A.  Kwakman PhD-candidate Gastro-enterology and Hepatology
R.  La Distia Nora PhD-candidate Immunology
W.B.  van  Leeuwen Senior researcher not being a workgroup leader Medical Microbiology & Infectious Disease
N.  Lemmens Technician Medical Microbiology & Infectious Disease
Wilson  Lim MSc student (please specify in remarks) Medical Microbiology & Infectious Disease
R.P.L.  Louwen Technician Medical and Tumor Immunology
M.M.  Mebius PhD-candidate Microbiology
A  van der   Meijden Technician Medical Microbiology
dr.  D.C.  Melles Physician (MD) Medical Microbiology & Infectious Disease
Dr.  T.H.M.  Mes Postdoc/junior researcher Virology
Dr  P.M.M.S.  Meyer Sauteur PhD-candidate Pediatrics
first-rate website  Tmmaverick  MiguelMeacy PhD-candidate General Surgery
M.T.M.  Mitul MSc student (please specify in remarks) Immunology
F. P. N.  Mollema PhD-candidate Medical Microbiology & Infectious Disease
drs  D.J.F.  Moojen PhD-candidate
MSc  SJCFM  Moorlag PhD-candidate Infectious Diseases
S E  Mudde MSc student (please specify in remarks) Infectious Diseases
MD  A.E.  Muller Physician (MD) Medical Microbiology & Infectious Disease
MD PhD  D.T.  Nguyen Physician (MD) Medical Microbiology & Infectious Disease
Dr.  H.N.  Niangaly MSc student (please specify in remarks) Epidemiology
Dr.  J.L.  Nouwen Associate professor (UHD) Medical Microbiology & Infectious Disease
Msc  Nyuykonge PhD-candidate Medical Microbiology & Infectious Disease
Mr.  J.J  MIScT  Oddoye Assistent professor (UD) Microbiology
BSc  M.D.O.  Oduber MSc student (please specify in remarks) Postgraduate School
N.M.A.O.  Okba PhD-candidate Virology
S.  Oktaria PhD-candidate Dermatology
A.H.A.G  Ooms Other as mentioned (please specify in remarks) Student
MSc.  R.G.  Otto Technician Medical Microbiology & Infectious Disease
E.D.  Pieterman PhD-candidate Medical Microbiology & Infectious Disease
J  Pirzadian PhD-candidate Medical Microbiology & Infectious Disease
Msc.  J.M.  Refos PhD-candidate Medical Microbiology & Infectious Disease
P.M.  den  Reijer PhD-candidate Medical Microbiology & Infectious Disease
Tmmaverick  richeventtver Workgroup leader within the School General Surgery
Ladyofrage  richeventvladimir Professor not being a workgroup leader General Surgery
N.A.R.M.  Rico Montanari MSc student (please specify in remarks) Postgraduate School
Paulpeter  Robertzex Professor not being a workgroup leader General Surgery
J.  Rodriguez-Coira Villanueva MSc student (please specify in remarks) Student
Dr.  A.M.C.  van  Rossum Physician (MD) Pediatrics
MSc.  C.  Saha PhD-candidate Medical Microbiology & Infectious Disease
MD  Y  R  Saharman PhD-candidate Medical Microbiology & Infectious Disease
ing.  W.J.  van de  Sande Technician Medical Microbiology & Infectious Disease
A.P. Sari  Sari MSc student (please specify in remarks) Gastro-enterology and Hepatology
M.J.  Sarink PhD-candidate Medical Microbiology & Infectious Disease
Drs.  T.  Schoffelen PhD-candidate Experimental Internal Medicine
MSc  AS  van der  Schoor PhD-candidate Medical Microbiology & Infectious Disease
G.J.  Sips Physician (MD) Medical Microbiology & Infectious Disease
Drs.  B.S.  Slingerland PhD-candidate Medical Microbiology & Infectious Disease
S.  Snijders Technician Medical Microbiology & Infectious Disease
H  van der   Spek Technician Medical Microbiology & Infectious Disease
Drs.  M.H.T.  Stappers PhD-candidate Medicine
K.R.  van  Straalen PhD-candidate Anaesthesiology
MSc.  J.W.  Swierstra PhD-candidate Medical Microbiology & Infectious Disease
MR  TANMOY PhD-candidate Medical Microbiology & Infectious Disease
MR  TANMOY Postdoc/junior researcher Medical Microbiology & Infectious Disease
M.J.  Tempelmans Plat-Sinnige PhD-candidate Medical Microbiology & Infectious Disease
T.D.K.  Thai Physician (MD) Medical Microbiology
Dr.  C.  van  Tienen Physician (MD) Medical Microbiology & Infectious Disease
MSc  E.H.  Tijsse-Klasen PhD-candidate Virology
J.  Top PhD-candidate Medical Microbiology & Infectious Disease
J.E.E.  Totté PhD-candidate Dermatology
W.W.J.U.  Unger Assistent professor (UD) Pediatrics
dr. ir.  S.J.C.  Verhaegh Postdoc/junior researcher Medical Microbiology & Infectious Disease
Drs.  J.H.  Verhagen PhD-candidate Virology
Drs.  N.J.  Verkaik PhD-candidate Medical Microbiology & Infectious Disease
Dr.  S  Verschuere PhD-candidate Pathology
MD  P.E.B.  Verwer PhD-candidate Medical Microbiology & Infectious Disease
MSc.  A.F.  Voor in 't holt PhD-candidate Medical Microbiology & Infectious Disease
drs.  S.M.C.A.  de  Walick PhD-candidate Medical Microbiology
dr.  W.J.B.  van  Wamel Assistent professor (UD) Medical Microbiology & Infectious Disease
MD  A. A.  Wattel Physician (MD) Medical Microbiology & Infectious Disease
dr  H.  Wertheim Senior researcher not being a workgroup leader Medical Microbiology & Infectious Disease
Ing  H.F.M.  Willemse - Erix Technician Medical Microbiology & Infectious Disease
R.  te  Witt PhD-candidate Medical Microbiology & Infectious Disease
A.  van der   Woude PhD-candidate Microbiology
E.  Wright PhD-candidate Infectious Diseases
MD  H.H.  van der  Zee PhD-candidate Immunology