Global transcriptional profiling of Candida albicans cwt1 null mutant

Abstract

CaCwt1p is a Candida albicans putative transcriptional factor homologue to Rds2p in Saccharomyces cerevisiae. The lack of this protein in S. cerevisiae leads to a pleiotropic resistance to drugs and defects in cell wall architecture that are also detectable in C. albicans. It is also known that CaCwt1p is mainly expressed in the stationary growth phase of this fungus. In order to elucidate the role of CWT1, transcriptome analysis of the mutant strain was performed in exponential and stationary growth phases. A total of 460 genes were found to be up- or downregulated in the mutant strain growing exponentially, and 666 genes presented a misregulation when cwt1 cells reached the stationary phase. Under both conditions, 6% of the genes were related to cell wall architecture. An important set of genes involved in protein translation and ribosome biogenesis presented altered expression levels in cwt1 in both exponential and stationary growing cells. In addition, genes encoding for glycolytic enzymes and glycerol formation were found to be differentially regulated throughout cell growth. Finally, the expression of other transcriptional factors was modified in cwt1. This fact could indicate that the pleiotropic phenotype presented by the cwt1 null mutant is not only due to its absence, but also to the modified expression of other transcriptional factors. RSAT software was used to predict theoretical DNA binding motifs for this transcriptional factor. Surprisingly, the DNA sequences AGGGCT and/or AGCCCT could act as a direct promoting binding site for Cwt1p. These sequences have been reported to be related to the STRE box.