Virulence and signal transduction of hypha formation in Candida albicans
The aims of this work were to investigate the signal transduction pathways controlling the yeast-hyphal morphological transition of Candida albicans, and to gain a clearer understanding of the importance of hyphal formation of the virulence of this organism. The work can be divided into two areas. Firstly, the recently discovered species Candida dubliniensis, the only species in addition to C. albicans capable of forming true non-constricted hyphae, was examined in comparison to C. albicans to compare their virulence capability in vitro and in vivo. The two species were compared with respect to hypha formation, adherence, possession of SAP genes and virulence in the mouse model of systemic candidosis. C. dubliniensis possessed at least a homologue to each of the nine known C. albicans SAP genes, adhered to human cells to a greater degree on exposure in glucose, formed hyphae slightly less efficiently than C. albicans and was less virulent in mice. C. dubliniensis has been isolated particularly from the mouths of HIV positive and AIDS patients. The results of the virulence assessment could be interpreted as reflecting its epidemiological occurrence, - increased adherence on exposure to glucose may be a response to dietary sugar and the reduced virulence would explain in part its association with immunocompromised hosts. Secondly, the role of phosphoinositide signalling in control of the yeast-hyphal transition was investigated by the cloning and characterisation of two putative phosphatidylinositol 4-kinase genes from C. albicans, named CaPIK1 and CaPIK2. Both genes were cloned through their homology to the S. cerevisiae PIK1 gene. Disruption of the CaPIK1 gene in C. albicans indicated that it had no obvious role in the control of hypha formation.