Physiological Studies on Candida albicans

Candida albicans is a polymorphic fungus that is capable of causing the life-threatening disease Candidiasis once it reaches the bloodstream of a susceptible host. One of the major virulence factors is its ability to switch from yeast to hyphal or pseudohyphal morphology. Yeast to hyphal transition is well studied and many environmental signals such as high temperature, alkaline pH, and presence of high CO2 level, serum, N-Acetyl Glucosamine regulate hyphal morphogenesis by several well studied signal transduction pathways. Yeast to pseudohyphal development is relatively less understood. Earlier we have reported that aromatic amino acids are utilized by C. albicans in poor nitrogen conditions by fusel oil pathway, and as a byproduct, aromatic alcohols are secreted outside the cell. Humans cannot synthesize all the three aromatic amino acids viz. phenylalanine, tyrosine, and tryptophan; and have to obtain them through diet. Fungal pathogen C. albicans must synthesize them and therefore their regulation is critical for virulence. Here we report that aromatic alcohols secreted by the fungus C. albicans, send a signal back to the cell, which derepress the transcriptional factor Gcn4p. We show that in the presence of aromatic alcohols, C. albicans stimulate pseudohyphae that are dependent on both Efg1p and Cph1p. Earlier our group reported that high phosphate levels also stimulated pseudohyphae. In this report we show that high phosphate levels derepress Gcn4p similar to the aromatic alcohols. Further analysis revealed that high phosphate levels stimulated pseudohyphae in cph1/cph1, efg1/efg1, and cph1/cph1 efg1/efg1 mutant cells as well. Our data suggest that high phosphate level stimulated pseudohyphal morphogenesis can be independent of MAPKinase pathway and cAMP/PKA pathway.