Transcriptome of Cryptococcus neoformans and Cryptococcus deneoformans
Ontology highlight
ABSTRACT: The goal of this study was to position all transcripts extremities in two species of Cryptococcus using TSS-Seq and QuantSeq 3' mRNA-Seq when cells are grown under different conditions. We analysed also the level of expression of each genes in the same condition using the same cell sample. All these data have spiked in using a fixed quantity of S. cereviae cells added just before DNA and RNA extraction.
ORGANISM(S): Cryptococcus neoformans Cryptococcus neoformans var. neoformans
Project description:We measured protein translation (by ribosome profiling) and RNA levels (by polyA-enriched RNA-seq) in Cryptococcus neoformans strain H99 and Cryptococcus neoformans strain JEC21. This is the first transcriptome-wide map of translation in this species complex.
Project description:We investigated the effects of the hypoxia-mimetic CoCl2 on the gene expression of pathogenic fungus Cryptococcus neoformans. Keywords: compound treatment design
Project description:Cryptococcus neoformans is a life-threatening basidiomycete fungal pathogen responsible for meningoencephalitis in immunocompromised patients. This yeast can adapt to diverse habitats, efficiently produces virulence factors, and escapes immune surveillance. This implies intricate mechanisms underlying its gene regulation networks, which are yet to be comprehensively understood. Alternative transcription usage regulation has been identified as the major mean for gene expression regulation in metazoans. However, in fungi, its impact remains elusive as its study has thus far been restricted to model yeasts. We here re-analysed transcription start site (TSS)-seq data to define genuine TSS clusters in two species of pathogenic Cryptococcus. We identified two types of TSS clusters associated with specific DNA sequence motifs. Our analysis also revealed that alternative TSS usage regulation in response to environmental cues is widespread in Cryptococcus, altering gene expression and protein targeting. Importantly, we performed a forward genetic screen to identify a unique transcription factor (TF) named Tur1, which regulates aTSS usage genome-wide when cells switch from exponential phase to stationary phase. Tur1 has been previously shown to be essential for virulence in C. neoformans. Accordingly, we demonstrated here that a tur1Δ mutant strain is more sensitive to superoxide stress and phagocytosed more efficiently by macrophages than the Wild-type (WT) strain.
Project description:We investigated the effects of the hypoxia-mimetic CoCl2 on the gene expression of pathogenic fungus Cryptococcus neoformans. Keywords: compound treatment design Three biological repeats were performed using three independent RNA sets isolated from cells cultured on different days and the dye-reverse hybridizations were performed for all three sets. One set of RNA was also subjected to technical repeats.
Project description:Cryptococcus neoformans is the most common cause of fungal meningitis, with high mortality and morbidity. The reason for the frequent occurrence of Cryptococcus infection in the central nervous system (CNS) is poorly understood. In this study, we find that inositol plays an important role in the transversal of Cryptococcus across the blood-brain barrier (BBB) both in an in vitro human BBB model and in vivo animal models. The inositol stimulation of BBB crossing is dependent upon fungal inositol transporters. The upregulation of genes involved in the inositol catabolism pathway is evident in a microarray analysis. The expression of CPS1, a gene encoding the hyaluronic acid synthase in Cryptococcus, is also upregulated by the inositol treatment. The production of hyaluronic acid increased in cells treated with inositol, which leads to the enhanced binding ability of Cryptococcus cells to the human brain microvascular endothelial cells (HBMECs) constituting the BBB. Overall, our studies provide a mechanism for inositol-dependent Cryptococcus transversal of the BBB, supporting our hypothesis that host inositol utilization by the fungus contributes to Cryptococcus CNS infection.
Project description:Light is a universal environmental signal perceived by many organisms, including the fungi in which light regulates both common and unique biological processes depending on the species. We conducted a whole-genome microarray analysis on the basidiomycete fungus Cryptococcus neoformans to identify light-regulated genes.
Project description:Cryptococcus neoformans (Cn) is an opportunistic fungal microorganism that causes life-threatening meningoencephalitis. During the infection, the microbial population is heterogeneously composed of cells with varying generational ages, with older cells accumulating during chronic infections. This is attributed to their enhanced resistance to phagocytic killing and tolerance of antifungals like fluconazole (FLC). Using RNA-seq, we investigated how transcriptomic changes in different aspects of metabolism contribute to age-associated FLC tolerance in Cn.
Project description:Cryptococcus neoformans is a life-threatening basidiomycete fungal pathogen responsible for meningoencephalitis in immunocompromised patients. This yeast can adapt to diverse habitats, efficiently produces virulence factors, and escapes immune surveillance. This implies intricate mechanisms underlying its gene regulation networks, which are yet to be comprehensively understood. Alternative transcription usage regulation has been identified as the major mean formeans of gene expression regulation in metazoans. However, in fungi, its impact remains elusive as its study has thus far been restricted to model yeasts. We Hhere we re-analysed transcription start site (TSS)-seq data to define genuine TSS clusters in two species of pathogenic Cryptococcus. We identified two types of TSS clusters associated with specific DNA sequence motifs. Our analysis also revealed that alternative TSS usage regulation in response to environmental cues is widespread in Cryptococcus, altering gene expression and protein targeting. Importantly, we performed a forward genetic screen to identify a unique transcription factor (TF) named Tur1, which regulates alternative TSS (aTSS) usage genome-wide when cells switch from exponential phase to stationary phase. Tur1 has been previously shown to be essential for virulence in C. neoformans. Accordingly, we demonstrated here that a tur1? mutant strain is more sensitive to superoxide stress and phagocytosed more efficiently by macrophages than the Wild-type (WT) strain.
Project description:Discovering the Roles of the Casein Kinase 2 Complex in the Growth, Differentiation, Stress Responses, and Pathogenicity of Cryptococcus neoformans
Project description:Invasive fungal infections (IFIs) are difficult to treat. Few effective antifungal drugs are available and many have problems with toxicity, efficacy and drug-resistance. To overcome these challenges, existing therapies may be enhanced using more than one agent acting in synergy. Previously, we have found amphotericin B (AMB) and the iron chelator, lactoferrin (LF), were synergistic against Cryptococcus neoformans and Saccharomyces cerevisiae. This study investigates the mechanism of AMB+LF synergy using RNA-seq in Cryptococcus neoformans H99.