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A fungal transcription regulator of vacuolar functions modulates Candida albicans interactions with host epithelial cells [RNA-seq]

ABSTRACT: We employed RNA-Seq to identify targets of regulation of the transcription regualtor ZCF8 in nitrogen-starved Candida albicans cells.

ORGANISM(S): Candida albicans

PROVIDER: GSE181653 | GEO | 2021/08/15

REPOSITORIES: GEO

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A fungal transcription regulator of vacuolar functions modulates Candida albicans interactions with host epithelial cells

Project description:We employed RNA-Seq to identify ZCF8-dependent and ZCF8-indepenent transcriptional changes in Candida albicans cells treated with nigericin.

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A fungal transcription regulator of vacuolar functions modulates Candida albicans interactions with host epithelial cells [ChIP-seq]

Project description:We employed ChIP-Seq to identiy direct targets of regulation of the Candida albicans transcription regulator Zcf8p.

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Comparative phenotypic analysis of the major fungal pathogens Candida parapsilosis and Candida albicans

Project description:Abstract: Candida parapsilosis and Candida albicans are human fungal pathogens that belong to the CUG clade in the Saccharomycotina. In contrast to C. albicans, relatively little is known about the virulence properties of C. parapsilosis, a pathogen particularly associated with infections of premature neonates. We describe here the construction of >200 C. parapsilosis strains carrying double allele deletions of transcription factors, protein kinases and species-specific genes. Two independent deletions were constructed for each target gene. Growth in > 40 conditions was tested, including carbon source, temperature, and the presence of antifungal drugs. The phenotypes were compared to C. albicans strains with deletions of orthologous transcription factors. We found that many phenotypes are shared between the two species, such as the role of Upc2 as a regulator of azole resistance. Others are unique. For example, Cph2 plays a role in the hypoxic response in C. parapsilosis and not in C. albicans. We found extensive divergence between the biofilm regulators of the two species. We identified 7 transcription factors and one protein kinase that are required for biofilm development in C. parapsilosis. Only three (Efg1, Bcr1, and Ace2) have similar effects on C. albicans biofilms, whereas Cph2, Czf1, Gzf3 and Ume6 have major roles in C. parapsilosis only. In addition, two transcription factors (Brg1 and Tec1) with well-characterized roles in biofilm formation in C. albicans do not have the same function in C. parapsilosis. We also compared the transcription profile of C. parapsilosis and C. albicans biofilms. Our analysis suggests the processes shared between the two species are predominantly metabolic.

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Project description:To infer transcriptional networks of nitrogen utilization , Candida albicans was exposed to nitrogen starvation for four hours and then offered arginine or BSA as sole nitrogen source. Time-series transcription data was obtained from both the starvation and the feeding periods, and the response to different nitrogen availability was used for network modelling with selected genes.

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Project description:Candida albicans is the most common human fungal pathogen causing mucosal and systemic infections, but human anti-fungal immunity remains poorly defined. Expression profiling of Candida-stimulated human peripheral blood mononuclear cells (PBMCs) provides new insights into Candida-specific host defense mechanisms in humans.

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Manganese homeostasis modulates fungal virulence and stress tolerance in Candida albicans

Project description:As transition metal availability is very limited inside the human host, fungal pathogens have evolved sophisticated mechanisms to uptake and utilize these micronutrients at the infection interface. While considerable attention was turned into iron, copper and zinc acquisition mechanisms and their importance in fungal fitness, less was done regarding either the role of Mn in infectious processes or the cellular mechanism by which fungal cells achieve their Mn-homeostasis. Here, we undertook a transcriptional profiling of the pathogenic fungus Candida albicans experiencing both Mn starvation and excess to comprehensibly capture biological processes that are modulated by Mn. We uncovered that Mn scarcity influence diverse biological processes associated with fungal fitness including morphogenetic switch, invasion of host cells and antifungal sensitivity. We also uncovered that Mn levels influence the abundance of iron and zinc emphasizing the complex crosstalk between ions metals. Deletion of SMF12, a member of Mn Nramp transporters confirmed its contribution to Mn uptake. In accordance with the RNA-seq data, smf12 was unable to form hyphae and damage host cells, and exhibited sensitivity to azole antifungals. We also found that unfolded protein response (UPR), likely activated by decreased glycosylation under Mn limitation, was essential to promote C. albicans growth. RNA-seq profiling of cells exposed to Mn excess uncovered that the UPR signaling was also essential to bypass Mn toxicity. Collectively, this study underscores the importance of Mn homeostasis in fungal virulence, and comprehensively provides a transcriptional portrait of biological functions that are modulated by Mn in a fungal pathogen.

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