Targeting the Achilles heel of fungi
Fungi such as Candida albicans and Aspergillus fumigatus constitute a major source of opportunistic infections in humans. Current antifungal chemotherapeutic agents are inadequate to treat life-threatening fungal infections. Therefore, there is an urgent need to generate new, efficacious, non-toxic compounds with broad-spectrum antifungal activity. As such, the fungal wall constitutes an attractive candidate for developing antifungal agents since its major components are absent from mammals. The cell wall core consists of the polysaccharides chitin and ß glucan which are cross-linked to each other. The focus of the EU-funded ‘The fungal cell wall as a target for antifungal therapies’ (Fungwall) project concentrated on the pathways of fungal cell wall polysaccharide synthesis, cross-linking and branching. Enzymes and reactions associated with these processes were thoroughly studied, novel targets were defined and a series of compounds that disrupt the fungal cell wall were screened. Also, the mechanisms involved in cell wall integrity maintenance and remodelling during morphogenesis were investigated. Fungwall outcomes demonstrated the potential of targeting the cell wall as a valid non-toxic approach for eradicating fungal infections. Commercial exploitation of the project deliverables is hoped to bring down the morbidity associated with fungal infections.
