Regulation of cell wall dynamics in Candida albicans by CPH1 and EFG1, two transcription factors essential for virulence

Cell wall dynamics in C. albicans, the most common fungal pathogen in man, underlie regulatory processes during the yeast- to-hyphae transition. To analyze this regulation on the transcriptional level we have established a DNA microarray representing genes implicated in cell wall biogenesis. These genes comprise both known and not yet further characterized open reading frames that share significant homologies to cell wall genes in C. albicans or S. cerevisiae. Using these microarrays we have determined transcriptional profiles of wildtype cells, delta efg1, delta cph1 and delta efg1/delta cph1 mutants grown under various conditions to induce yeast or hyphal growth in C. albicans. We were able to identify several novel genes that are differentially transcribed in yeast and hyphal forms of C. albicans and we could show that EFG1 but not CPH1 plays a major role in the transcriptional regulation of cell wall components. Cluster analysis using the algorithm by Eisen et al. revealed at least three major clusters of genes. Cluster I comprised genes that were upregulated in hyphae compared to yeast cells. Neither EFG1 nor CPH1 were essential for their transcription. Genes that were upregulated in hyphae with a strictly EFG1 but not CPH1 dependent transcription were assigned to Cluster II. At least three yet not further characterized genes were attributed to Cluster III. These genes were transcribed in the yeast form and were downregulated in hyphae in an EFG1 dependent manner.