Elucidating the impact of loss of function of AP-2 endocytic adaptor complex of Candida albicans in hyphal morphology switch and virulence during host - pathogen interactions.

Recently AP-2 endocytic adaptor complex was determined to have an important role in the endocytosis of an important Candida albicans cell wall synthase, chitin synthase 3 (Chs3). Loss of function of AP-2 cells cannot endocytose Chs3 resulting in increased cell wall composition changes and defects during polarized growth. The cell wall and hyphal switch are two important C. albicans virulence factors so studying the impact of AP-2 was of interest. In this study, the importance of AP-2 for the host – pathogen interactions of the human pathogenic fungus C. albicans were investigated. Three infection models were used (macrophages, epithelial and zebrafish embryos) to investigate the significance of AP-2 during host-pathogen interactions. This investigation shows that the cell wall composition changes in C. albicans with loss of function of AP-2 resulting in increased phagocytosis by macrophages, decreased host adhesion and decreased virulence in both macrophage and zebrafish models. C. albicans with loss of function of AP-2 complex are less virulent however they are not cleared by the host immune system but rather proliferate in the host cells. The mutant C. albicans cells were less invasive than wild type cells during epithelial infections, suggesting reduced host cell damage and virulence. This thesis concludes that the AP-2 is critical for the virulence of C. albicans cells due to its role in cell wall remodelling, hyphal morphology switch and hyphal maintenance.