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The Fungal cell wall as a target for antifungal therapies

Final Report Summary - FUNGWALL (The Fungal cell wall as a target for antifungal therapies)

The cell wall of pathogenic fungi is a good target for the development of new drugs for the following reasons:
(1) The fungal cell wall is required for fungal cell integrity and is essential for fungal growth and for virulence;
(2) Polysaccharidic components of the cell wall are unique to fungi and consequently, putative inhibitors of the biosynthetic pathways responsible for cell wall construction can be potent antifungals, as shown by the recent launch by big Pharmas of drugs inhibiting ß1-3 glucan synthesis.

The FUNGWALL objectives were centred on the assembly of the cell wall polysaccharide skeleton. The enzymes and reactions associated with chitin, ß glucan and mannan synthesis, ß glucan cross-linking and branching will be investigated. New post genomic approaches will enable us to first revisit old targets, define novel targets and to screen for novel compounds that disrupt the integrity of the cell wall with the goal of identifying new generation antifungals that target fungal cell wall biosynthesis. These studies will use primarily the two main fungal pathogens in Europe, Candida albicans and Aspergillus fumigatus.

Significant progress has been made in all the Work packages (WPs) presented. Over the 3-year period, 75 % of the deliverables were completed. Two reasons can be put forward to explain the lack of completion of 100 % of the deliverables. First, for some of the deliverables, the impossibility to complete them was due to technological issues. For the other deliverables, the full success has inevitably been affected by the failure of the European Commission to grant a no-cost extension that would have allowed several of the partners to work for a true 36-month term for the project.

Project achievements have placed Europe in a leading position in the world for the analysis of fungal cell wall. The coupling of biochemical and genetical methodologies was extremely synergetic to tackle this problem and have given a unique flavour to our STREP. A close contract between the different members of the STREP will now continue and will lead to new scientific developments in the area. We hope that this collaboration will continue to be supported by Europe.

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