The roles of calcium and calmodulin in the regulation of dimorphism and pathogenicity of Candida albicans
Studies on the capacity of growing and non-growing cells to be induced to grow in different morphological forms suggested that metabolically active cells are better able to undergo dimorphism than metabolically quiescent cells. Accelerated growth kinetics requiring de novo RNA and or protein biosynthesis but not DNA synthesis were observed in metabolically active cells undergoing a yeast to hyphal transition. The roles that divalent cation calcium plays in eukaryotic growth and morphogenesis are illustrated in this study with regard to C. albicans. Free calcium was required for germ tube emergence from stationary phase yeast cells but not for subsequent growth or hyphal extension. The galvanotropic response of C. albicans hyphae was investigated and was shown to be quantitatively dependent on the concentration of available calcium in the medium and also on the integrity of calcium dependent second messenger systems. The mechanism of galvanotropism of C. albicans may be due to the electrophoretic movement of charged proteins, possibly calcium transport channels, in the plasma membrane as shown by the dependence of cathodotropic growth on external pH. Although the yeast to hyphal transition can be easily controlled and studied in vitro, attempts to use such methods to control morphological development, with a view to comparing the relative infectivity of each morphology, are complicated in the environment in vivo. Yeast cells were introduced into the rat vagina, or systemically into mice, along with chemical effectors which had been shown to prevent the yeast to mycelial transition in vitro without affecting the growth rate of the cells per se. It was concluded tentatively from this study, that, in the rat vaginal model of candidosis, the hyphal form of growth is better adapted and more pathogenic than the yeast form.