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Infections due to bacteria, fungi and parasites: diagnosis, molecular...

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Title Infections due to bacteria, fungi and parasites: diagnosis, molecular mechanisms, epidemiology, therapy and prevention
Period 01 / 2008 - unknown
Status Completed
Research number OND1281063
Data Supplier Website MolMed

Abstract

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.

Related organisations

Related people

Project leader Prof.dr. A. van Belkum
Project leader Prof.dr. H.P. Endtz

Classification

A73000 Primary health care and second-line health care
A76000 Patients care
D21800 Immunology, serology
D22100 Microbiology
D23110 Infections, parasitology
D24200 Health education, prevention

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