Pathogenicity and Dimorphism in Candida Albicans
thesisposted on 09.12.2010, 11:20 by Alan Cockayne
The aims of this study were to extend existing knowledge of the interactions of the growth environment and morphological development in C.albicans, to investigate polysaccharide composition in relation to cell shape and age and to consider the significance of dimorphism in relation to the pathogenesis of candidosis. It was impossible to identify any single environmental factor responsible for the control of the complex morphological development of C.albicans. Many factors appeared to initiate germ tube formation but subsequent growth of the fungus into branched hyphae or unbranched hyphae with secondary blastospores was dependent and influenced by the atmosphere of incubation. The imidazole antifungal, ketoconazole, at low concentrations, was found to inhibit hyphal branching in C.albicans completely. The antifungal had no effect on germ tube initiation or blastospore budding. Some inhibition of cell growth was, however, observed under conditions that favoured mycelium production or blastospore budding. The polysaccharide composition of C.albicans was found to be morphology-and age related and was shown to be affected by the composition of the growth medium. Chitin content of C.albicans increased during germ tube initiation and hypha formation. Blastospore budding and secondary blastospore production were associated with a fall in chitin content. Although the activity of the enzyme chitin synthase correlated well with chitin content in germ tubes and blastospores, no correlation was found between enzyme activity and hyphal branching. Phagocytosis and intracellular killing of standardized biomasses of blastospores, germ tubes and hyphae by human polymorphs and mouse peritoneal macrophages were investigated in an objective radiolabel assay. Blastospores, germ tubes and hyphae were phagocytosed to a similar extent by human polymorphs. Blastospores were, however, less efficiently killed than the filamentous forms and initial resistance to killing did not appear to be related to intracellular germ tube production. C.albicans antiserum did not significantly affect the efficiency of phagocytosis and killing by human polymorphs. Serum antibody and complement, however, appeared to be involved in these processes. Mouse peritoneal macrophages were less efficient than human polymorphs at phagocytosing and killing C.albicans.