Identification of cell cycle-regulated, putative hyphal genes in Candida albicans.

Candida albicans, a major fungal pathogen in human, can grow in a variety of morphological forms ranging from budding yeast to pseudohyphae and hyphae, and its ability to transition to true hyphae is critical for virulence in various types of C. albicans infections. Here, we identify 17 putative hyphal genes whose expression peaks during the S/G2 transition of the cell cycle in C. albicans . These genes are Candida-specific (i.e., they do not have orthologs in S.cerevisiae, a related fungal species that does not exhibit hyphal growth and is primarily non-pathogenic), and their promoters are enriched for the DNA binding site motifs of Tec1 and Rfg1, two transcription factors (TFs) known to play important roles in hyphal growth and virulence. For 5 of the 17 genes we found strong evidence in the literature that confirms our hypothesis that these genes are involved in hyphal growth and/or virulence, for 5 additional genes we found suggestive (albeit weak) evidence, while the other genes remain to be tested. It will be interesting to determine in future studies whether these 17 putative hyphal genes, whose expression peaks during the S/G2 transition, are part of a mechanism for this pathogenic fungus to 'turn on' hyphal growth late during the cell cycle, or if these genes are used to sustain hyphal growth and ensure that the cell does not transition back to yeast growth. In either case, the involvement of these genes in hyphal growth makes them putative targets for new antifungal drugs aimed at inhibiting hyphae formation in C. albicans.