The Iron Chelator BPS is a Novel Inducer of Hyphal Morphogenesis in Candida albicans

Candida albicans is a commensal fungus that is also an increasingly important cause of systemic infections among immunocompromised individuals, with crude morality rates of 35-60%. The ability of C. albicans to undergo a reversible morphological transition from yeast (oval shaped cells) to hyphae (elongated, filamentous cells) in response to a variety of external stimuli has been long associated with the virulence and pathogenesis of C. albicans. Well-characterized stimuli include elevated temperature (37°C), exposure to serum, to N-acetylglucosamine, alkaline pH, CO₂, and growth in low-nitrogen media, among others. We identified bathophenanthroline disulfonic acid (BPS), a commonly used iron chelator, as another inducer of hyphal growth. The iron chelator ferrozine, in contrast, does not induce hyphal growth. Since BPS inhibits cellular growth due to iron chelation, addition of hemin or hemoglobin as alternative iron sources best enable to follow the BPS-induced hyphal morphogenesis, but these compounds do not seem to be directly involved in the morphogenetic effect of BPS. Addition of iron or of copper, an alternative BPS ligand, can abolish the morphogenetic effect of BPS. We hypothesize that BPS induces hyphal growth either by binding to a receptor or by its ability, not shared with other iron chelators, to penetrate the cells in its free form. Genetic analysis of BPS-induced morphogenesis is currently being carried out.