The Flo8 Transcription Factor Is Essential for Hyphal Development and Virulence in Candida albicans□D
نویسندگان
چکیده
The transcription factor Flo8 is essential for filamentous growth in Saccharomyces cerevisiae and is regulated under the cAMP/protein kinase A (PKA) pathway. To determine whether a similar pathway/regulation exists in Candida albicans, we have cloned C. albicans FLO8 by its ability to complement S. cerevisiae flo8. Deleting FLO8 in C. albicans blocked hyphal development and hypha-specific gene expression. The flo8/flo8 mutant is avirulent in a mouse model of systemic infection. Genome-wide transcription profiling of efg1/efg1 and flo8/flo8 using a C. albicans DNA microarray suggests that Flo8 controls subsets of Efg1-regulated genes. Most of these genes are hypha specific, including HGC1 and IHD1. We also show that Flo8 interacts with Efg1 in yeast and hyphal cells by in vivo immunoprecipitation. Similar to efg1/efg1, flo8/flo8 and cdc35/cdc35 show enhanced hyphal growth under an embedded growth condition. Our results suggest that Flo8 may function downstream of the cAMP/PKA pathway, and together with Efg1, regulates the expression of hypha-specific genes and genes that are important for the virulence of C. albicans.
منابع مشابه
The Flo8 transcription factor is essential for hyphal development and virulence in Candida albicans.
The transcription factor Flo8 is essential for filamentous growth in Saccharomyces cerevisiae and is regulated under the cAMP/protein kinase A (PKA) pathway. To determine whether a similar pathway/regulation exists in Candida albicans, we have cloned C. albicans FLO8 by its ability to complement S. cerevisiae flo8. Deleting FLO8 in C. albicans blocked hyphal development and hypha-specific gene ...
متن کاملDown-Regulation of the ALS3 Gene as a Consequent Effect of RNA-Mediated Silencing of the EFG1 Gene in Candida albicans
Background: The most important virulence factor which plays a central role in Candida albicans pathogenesis is the ability of this yeast to alternate between unicellular yeast and filamentous hyphal forms. Efg1 protein is thought to be the main positive regulating transcription factor, which is responsible for regulating hyphal-specific gene expression under most conditions. ALS3 is one of the ...
متن کاملRegulation of the Candida albicans Hypha-Inducing Transcription Factor Ume6 by the CDK1 Cyclins Cln3 and Hgc1
The ability to switch between proliferation as yeast cells and development into hyphae is a hallmark of Candida albicans. The switch to hyphal morphogenesis depends on external inducing conditions, but its efficiency is augmented in stationary-phase cells. Ume6, a transcription factor that is itself transcriptionally induced under hypha-promoting conditions, is both necessary and sufficient for...
متن کاملCrk1, a novel Cdc2-related protein kinase, is required for hyphal development and virulence in Candida albicans.
Both mitogen-activated protein kinases and cyclin-dependent kinases play a role in hyphal development in Candida albicans. Using an oligonucleotide probe-based screen, we have isolated a new member of the Cdc2 kinase subfamily, designated Crk1 (Cdc2-related kinase). The protein sequence of Crk1 is most similar to those of Saccharomyces cerevisiae Sgv1 and human Pkl1/Cdk9. In S. cerevisiae, CRK1...
متن کاملIdentification 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 . Th...
متن کامل