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Integrated post-genomic approaches for the understanding, detection and prevention of antifungal drug resistance in fungal pathogens

Integrated post-genomic approaches for the understanding, detection and prevention of antifungal drug resistance in fungal pathogens

Objective

The EURESFUN (European RESistance FUNgal) network will utilize genomics-based integrated approaches to study antifungal resistance in relevant fungal pathogens (Candida, Aspergillus). This network will study distinct resistance mechanisms (target mutations , drug efflux, signal transduction, transcriptional activation, cell wall alterations, biofilm formation) all of which can contribute individually or in combination to antifungal resistance in clinical isolates. Using microarray strategies, systematic dele tion/overexpression approaches, the network will also elucidate new resistance mechanisms. This approach will unravel potential novel targets for antifungal drug discovery, but also yield diagnostic tools and mutations suitable for the use in resistance mo nitoring and surveillance. Gene deletion approaches will infer new therapeutic strategies to improve efficacy of existing antifungal therapy, including combination drug therapies to generate synergism. Novel intervention strategies to minimise or bypass re sistance will be validated using animal models. Based on this knowledge, cell-based assays for drug target genes will be established and. used for drug discovery by a SME. To monitor progression of systemic infections and monitor resistance, the consortium will establish a collection of clinical strains representing ä wide range of antifungal susceptibilities. SMEs will pursue the development and validation of reliable diagnostic tools with commercial potential for rapid clinical strain identification and r esistance testing, employing microarray technologies in combination with PCR technologies. Finally this network will establish data on resistance incidence and prevalence and will link clinical data on susceptibility to known antifungals with therapy outco me. Major European reference centers will jointly set up and recommend European standards for resistance definition,resistance testing/prediction/definition,and breakpoint identification

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Coordinator

CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS

Address

Rue Du Bugnon 48
Lausanne

Switzerland

Administrative Contact

Dominique SANGLARD (Professor)

Participants (9)

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INSTITUT PASTEUR

France

UNIVERSITY OF WALES SWANSEA

United Kingdom

ISTITUTO DE SALUD

Spain

THE UNIVERSITY COURT OF THE UNIVERSITY OF ABERDEEN

United Kingdom

GATC BIOTECH AG

Germany

F2G LIMITED

United Kingdom

FRAUNHOFER-GESELLSCHAFT ZUR FÖRDERUNG DER ANGEWANDTEN FORSCHUNG E.V.

Germany

MEDIZINISCHE UNIVERSITÄT WIEN

Austria

UNIVERSITÄTSMEDIZIN GÖTTINGEN - GEORG-AUGUST-UNIVERSITÄT GÖTTINGEN - STIFTUNG ÖFFENTLICHEN RECHTS

Germany

Project information

Grant agreement ID: 518199

  • Start date

    1 December 2005

  • End date

    28 February 2009

Funded under:

FP6-LIFESCIHEALTH

  • Overall budget:

    € 3 777 733

  • EU contribution

    € 2 755 000

Coordinated by:

CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS

Switzerland