A CANDIDA-ALBICANS RAS-RELATED GENE (CARSR1) IS INVOLVED IN BUDDING, CELL MORPHOGENESIS AND HYPHA DEVELOPMENT

Candida albicans, the most important human fungal pathogen, is a dimor phic fungus that can grow either as a yeast or as a hyphal form in res ponse to medium conditions. A RAS-related C. albicans gene (CaR5R1) wa s isolated as a suppressor of a cdc24(ts) bud-emergence mutation of th e baker's yeast, Saccharomyces cerevisiae. The deduced protein encoded by CaRSR1 is 248 amino acids long and 56% identical to that encoded b y the S. cerevisiae RSR1 (BUD1) gene. Disruption of CaRSR1 in C. albic ans indicated that CaRSR1 is involved in both yeast and hypha developm ent. In the yeast phase, CaRSR1 is required for normal (polar) bud sit e selection and is involved in cell morphogenesis; in the yeast-myceli al transition it is involved in germ tube emergence; and in the develo pment of the hyphae it is involved in cell elongation. The disruption of CaRSR1 leads to reduced virulence in both heterozygote and homozygo te disruptants in a dose-dependent manner. The reduced virulence can b e attributed to the reduced germination and shorter hyphae resulting f rom the disruption of CaRSR1.