Candida albicans: Morphogenesis and Pathogenesis

Germ tube production of Candida albicans is favoured by, and is adapted to, conditions of nutrient deprivation, particularly low nitrogen. Hyphal development in media containing low serum concentrations is characterised by the formation of sparsely branched hyphae in which uninucleated, highly vacuolated intercalary compartments are arrested in the cell cycle, probably in G1. Re-entry into the cell cycle is accelerated by enrichment of the medium for nutrients and is preceded by reduction of the vacuolar space and concomitant increase in the size of the cytoplasmic volume. Hyphae exhibit contact guidance (thigmotropism) which may facilitate the invasion of tissues through local wounds, invaginations or sites of weakened surface integrity. Thus hyphal growth is adapted for nutrient scavenging and penetration of irregular surfaces.The genetics of dimorphism and virulence has been investigated through studies of differential gene expression, and by specific manipulation of gene expression by overexpression and the creation of null mutants. The expression of many genes is regulated during dimorphism however few of these play active roles in the regulation of morphogenesis. Disruption of genes encoding certain secreted aspartyl proteinases (SAP2) and a key step in the assembly of O-linked mannosylation (MNT1) led to attenuation of virulence. Manipulation of the expression of a hyphal specific gene HYR1 did not affect germ tube growth while overexpression of a constitutively expressed Candida gene HST7 stimulated pseudohyphal growth in Saccharomyces. Therefore, analysis and manipulation of the normal temporal pattern of gene expression is yielding valuable information regarding the regulation of morphogenesis and pathogenesis in this fungus.