Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Gordan R

PROVIDER: S-EPMC3331874 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Gordân Raluca R Pyne Saumyadipta S Bulyk Martha L ML

Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing 20120101

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 spec ...[more]

PMID: 22174285

Similar Datasets

Project description:The opportunistic human fungal pathogen, Candida albicans, undergoes morphological and transcriptional adaptation in the switch from commensalism to pathogenicity. Although previous gene-knockout studies have identified many factors involved in this transformation, it remains unclear how these factors are regulated to coordinate the switch. Investigating morphogenetic control by post-translational phosphorylation has generated important regulatory insights into this process, especially focusing on coordinated control by the cyclin-dependent kinase Cdc28. Here we have identified the Fkh2 transcription factor as a regulatory target of both Cdc28 and the cell wall biosynthesis kinase Cbk1, in a role distinct from its conserved function in cell cycle progression. In stationary phase yeast cells 2D gel electrophoresis shows that there is a diverse pool of Fkh2 phospho-isoforms. For a short window on hyphal induction, far before START in the cell cycle, the phosphorylation profile is transformed before reverting to the yeast profile. This transformation does not occur when stationary phase cells are reinoculated into fresh medium supporting yeast growth. Mass spectrometry and mutational analyses identified residues phosphorylated by Cdc28 and Cbk1. Substitution of these residues with non-phosphorylatable alanine altered the yeast phosphorylation profile and abrogated the characteristic transformation to the hyphal profile. Transcript profiling of the phosphorylation site mutant revealed that the hyphal phosphorylation profile is required for the expression of genes involved in pathogenesis, host interaction and biofilm formation. We confirmed that these changes in gene expression resulted in corresponding defects in pathogenic processes. Furthermore, we identified that Fkh2 interacts with the chromatin modifier Pob3 in a phosphorylation-dependent manner, thereby providing a possible mechanism by which the phosphorylation of Fkh2 regulates its specificity. Thus, we have discovered a novel cell cycle-independent phospho-regulatory event that subverts a key component of the cell cycle machinery to a role in the switch from commensalism to pathogenicity.

Project description:Nrg1 is a repressor of hypha formation and hypha-associated gene expression in the fungal pathogen Candida albicans. It has been well studied in the genetic background of the type strain SC5314. Here, we tested Nrg1 function in four other diverse clinical isolates through an analysis of nrg1Δ/Δ mutants, with SC5314 included as a control. In three strains, nrg1Δ/Δ mutants unexpectedly produced aberrant hyphae under inducing conditions, as assayed by microscopic observation and endothelial cell damage. The nrg1Δ/Δ mutant of strain P57055 had the most severe defect. We examined gene expression features under hypha-inducing conditions by RNA-sequencing (RNA-Seq) for the SC5314 and P57055 backgrounds. The SC5314 nrg1Δ/Δ mutant expressed six hypha-associated genes at reduced levels compared with wild-type SC5314. The P57055 nrg1Δ/Δ mutant expressed 17 hypha-associated genes at reduced levels compared with wild-type P57055, including IRF1, RAS2, and ECE1. These findings indicate that Nrg1 has a positive role in hypha-associated gene expression and that this role is magnified in strain P57055. Remarkably, the same hypha-associated genes affected by the nrg1Δ/Δ mutation in strain P57055 were also naturally expressed at lower levels in wild-type P57055 than those in wild-type SC5314. Our results suggest that strain P57055 is defective in a pathway that acts in parallel with Nrg1 to upregulate the expression of several hypha-associated genes. IMPORTANCE Hypha formation is a central virulence trait of the fungal pathogen Candida albicans. Control of hypha formation has been studied in detail in the type strain but not in other diverse C. albicans clinical isolates. Here, we show that the hyphal repressor Nrg1 has an unexpected positive role in hypha formation and hypha-associated gene expression, as revealed by the sensitized P57055 strain background. Our findings indicate that reliance on a single type strain limits understanding of gene function and illustrate that strain diversity is a valuable resource for C. albicans molecular genetic analysis.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets