Dataset Information

Tcc1p, a novel protein containing the tetratricopeptide repeat motif, interacts with Tup1p to regulate morphological transition and virulence in Candida albicans.

ABSTRACT: The transcriptional factor CaTup1p represses many genes involved in intracellular processes, including the yeast-hypha transition, in the human fungal pathogen Candida albicans. Using tandem affinity purification technology, we identified a novel protein that interacts with CaTup1p, named Tcc1p (Tup1p complex component). Tcc1p is a C. albicans-specific protein with a 736-amino-acid polypeptide with four tetratricopeptide repeat (TPR) motifs in the N-terminal portion. Tcc1p formed a protein complex with CaTup1p via the TPR domain of Tcc1p, independently of CaSsn6p-CaTup1p The tcc1Delta disruptant showed filamentous growth under conditions inducing the yeast form, as is true of the Catup1Delta mutant. Consistent with this result, the common set of hypha-specific genes was negatively regulated by both TCC1 and CaTUP1. These observations will provide new insights into CaTup1p-dependent transcriptional gene regulation in C. albicans.

SUBMITTER: Kaneko A

PROVIDER: S-EPMC1694794 | biostudies-literature | 2006 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tcc1p, a novel protein containing the tetratricopeptide repeat motif, interacts with Tup1p to regulate morphological transition and virulence in Candida albicans.

Kaneko Aki A Umeyama Takashi T Utena-Abe Yuki Y Yamagoe Satoshi S Niimi Masakazu M Uehara Yoshimasa Y

Eukaryotic cell 20060922 11

The transcriptional factor CaTup1p represses many genes involved in intracellular processes, including the yeast-hypha transition, in the human fungal pathogen Candida albicans. Using tandem affinity purification technology, we identified a novel protein that interacts with CaTup1p, named Tcc1p (Tup1p complex component). Tcc1p is a C. albicans-specific protein with a 736-amino-acid polypeptide with four tetratricopeptide repeat (TPR) motifs in the N-terminal portion. Tcc1p formed a protein compl ...[more]

PMID: 16998076

Similar Datasets

Project description:UnlabelledCandida albicans is the most prevalent fungal pathogen of humans, causing a variety of diseases ranging from superficial mucosal infections to deep-seated systemic invasions. Mucus, the gel that coats all wet epithelial surfaces, accommodates C. albicans as part of the normal microbiota, where C. albicans resides asymptomatically in healthy humans. Through a series of in vitro experiments combined with gene expression analysis, we show that mucin biopolymers, the main gel-forming constituents of mucus, induce a new oval-shaped morphology in C. albicans in which a range of genes related to adhesion, filamentation, and biofilm formation are downregulated. We also show that corresponding traits are suppressed, rendering C. albicans impaired in forming biofilms on a range of different synthetic surfaces and human epithelial cells. Our data suggest that mucins can manipulate C. albicans physiology, and we hypothesize that they are key environmental signals for retaining C. albicans in the host-compatible, commensal state.ImportanceThe yeast Candida albicans causes both superficial infections of the mucosa and life-threatening infections upon entering the bloodstream. However, C. albicans is not always harmful and can exist as part of the normal microbiota without causing disease. Internal body surfaces that are susceptible to infection by C. albicans are coated with mucus, which we hypothesize plays an important role in preventing infections. Here, we show that the main components of mucus, mucin glycoproteins, suppress virulence attributes of C. albicans at the levels of gene expression and the corresponding morphological traits. Specifically, mucins suppress attachment to plastic surfaces and human cells, the transition to cell-penetrating hyphae, and the formation of biofilms (drug-resistant microbial communities). Additionally, exposure to mucins induces an elongated morphology that physically resembles the mating-competent opaque state but is phenotypically distinct. We suggest that mucins are potent antivirulence molecules that have therapeutic potential for suppressing C. albicans infections.

Project description:The dimorphic fungus Candida albicans is one of the most important opportunistic pathogens for humankind. The use of fungicides against Candida could be associated with sub-inhibitory effects, which are referred to as fungal stress responses and are undesirable for the host. In this work, we investigated the antifungal action of 2,4-diacetylphloroglucinol (2,4-DAPG) against Candida albicans ATCC 10231 with a focus on their biofilm-forming ability. We found that 2,4-DAPG was able to reduce the ability of Candida cells to form biofilms, but complete inhibition and eradication effects were not achieved. Furthermore, C. albicans cells in the adherent state were characterized by reduced susceptibility to 2,4-DAPG compared to planktonic cells. The investigation of the mechanisms that could explain the antibiofilm action of 2,4-DAPG revealed a reduction in the cell`s surface hydrophobicity and the inhibition of the yeast-to-hyphae transition. The inhibition of the Candida cells filamentation was accompanied by an increase in the expression of the NRG1 gene, which is a negative regulator of hyphal development. In addition, we microscopically visualized the treated biofilms and revealed numerous channels that were decorated with particles and localized on the hyphae. We assumed that these hyphal structures could be associated with the secretion of aspartyl proteases (Sap). The performed assessments revealed an increase in the activity of Sap, which was accompanied by an increase in the expression of the sap2 and sap4 genes. The antifungal action of 2,4-DAPG is known to be associated with affecting the permeability of cellular structures, which leads to H+ATPase malfunction and the disruption of mitochondrial respiration. The subsequent cytosol acidification and generation of ROS trigger the inhibition of Candida filamentation and activation of Sap production. The introduction of antioxidant Trolox simultaneously with 2,4-DAPG leads to a reduction in Sap production. Collectively, the obtained data indicate new aspects of the interaction of fungal cells with 2,4-DAPG, an antimicrobial metabolite of Pseudomonas spp.

Dataset Information

Tcc1p, a novel protein containing the tetratricopeptide repeat motif, interacts with Tup1p to regulate morphological transition and virulence in Candida albicans.

Publications

Tcc1p, a novel protein containing the tetratricopeptide repeat motif, interacts with Tup1p to regulate morphological transition and virulence in Candida albicans.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets