EURESFUN – EUropean RESistance FUNgal

The elucidation of resistance

Printing process of a DNA microarray
Figure 1. Printing process of a DNA microarray using 8 pins.

As a result of modern, immunosuppressive therapies as well as a population which is rapidly aging, there is an ever increasing patient population that is susceptible to invasive fungal infections. Fungal infections are linked to a high mortality rate particularly in immunosuppressed patients. Since the standard diagnosis for pathogenic yeast and mold fungi is comparatively protracted and error-prone, prophylactic and expensive administration of antimycotics occurs with increasing frequency in hospitals. In the last several years reports of antimycotic resistances, particularly for Candida ssp., have increased steadily.

Conventional clinical tests for the identification of microorganisms and documentation of sensitivity or resistances to antimycotics rely on culture-based procedures (Microdilution, Etest®) and can require up to 14 days particularly for molds. However, the culturing of molds from patient samples is frequently unsuccessful even though the patient is definitely clinically suspicious. In these cases a therapy on suspicion, which cannot be specifically adapted to the relevant pathogen, has to be initiated. Furthermore, clinical studies have shown that phenotypical resistance testing contains an error of up to 15 %.

Precise diagnosis using DNA microarrays

 DNA microarray for the detection of point mutations
Figure 2: DNA microarray for the detection of point mutations in pathogenic fungi.

In order to detect human pathogenic fungi and their resistance spectrum quickly and accurately, a DNA microarray (Fig. 1) was developed at Fraunhofer IGB in the scope of the EU-funded joint project EURESFUN (European Resistance Fungal Network). Compared to customary culture-based methods, the DNA microarray technology has the advantage that numerous parameters can be concurrently tested. In addition to the identification of the 35 most frequent fungus species, point mutations can be monitored with this microarray that are responsible for the development of a resistance to fluconazole in C. albicans. Fluconazole is one of the most frequently administered antimycotics (Fig. 2). The functionality of the developed arrays could be tested and validated with clinical samples.

Project partners

  • Coordinator: Centre Hospitalier Universitaire Vaudois, Institut de Microbiologie (IMUL), Lausanne (Schweiz)
  • Unité Biologie Pathogénicité Fongiques , Institut Pasteur, Paris
  • Max F. Perutz Laboratories (Medizinische Universität Wien und Universität Wien)
  • Universitätsmedizin Göttingen - Georg-August-Universität Göttingen: Abteilung Medizinische Mikrobiologie (Bakteriologie)
  • University of Wales Swansea (UK)
  • Istituto de Salud Carlos III, Servicio de Micologia, Centro Nacional de Microbiologia, Madrid (Spanien)
  • The University Court of the University of Aberdeen (UK)
  • GATC Biotech AG, Konstanz
  • F2G Limited, Manchester (UK)

Term: Started in December 2005 - ended in November 2008

Funding

We would like to thank the European Union for funding the "EURESFUN" project in the scope of the Sixth Framework Program.