DEVELOPMENT OF PROTEIN-BASED ANTIFUNGALS

Abstract

Amongst the pathogenic and medically important fungi, Candida stands out as the only fungi of the top ten pathogens in healthcare associated infections. Healthy individuals have an effective immune defence against invasive mycosis but a compromised immunity resulting from disease or particular treatments renders one vulnerable to opportunistic fungal infection from the once innocuous fungi in the environment like Aspergillus fumigatus and commensal ones like Candida albicans. Treatment for invasive mycosis is limited to only a small selection of molecular drugs like Amphotericin B, Fluconazole and Caspofungin but they have their own shortcomings. The field of antifungal biologic therapy is relatively unexplored given the orphan status of invasive mycosis. Antifungal biologics offer the possibility of treating invasive mycosis both in systemic and tissue infections without the associated limitations facing conventional small molecule antifungals. This thesis aims to explore the relationship between the Pattern Recognition Receptor Dectin1 used by immune cells to recognize the Pathogen Associated Molecular Pattern β-glucan to develop Dectin-1 based biopharmaceuticals against the common fungal pathogen Candida albicans as a model for the use of PRR-PAMP natural affinity as a strategy against fungal infections.