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CoCl2 Response in Cryptococcus neoformans

ABSTRACT: We investigated the effects of the hypoxia-mimetic CoCl2 on the gene expression of pathogenic fungus Cryptococcus neoformans. Keywords: compound treatment design

ORGANISM(S): Cryptococcus neoformans

PROVIDER: GSE11390 | GEO | 2009/05/01

SECONDARY ACCESSION(S): PRJNA106511

REPOSITORIES: GEO

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CoCl2 Response in Cryptococcus neoformans

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.

2010-05-19 | E-GEOD-11390 | biostudies-arrayexpress

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Project description:CoCl2 Response in Cryptococcus neoformans

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Ribosome profiling of Cryptococcus neoformans H99

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.

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Light-regulated genes in Cryptococcus neoformans

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. Two-condition experiment, cells grown in complete darkness or exposed to white light. Six biological replicates independently grown and harvested. One replicate per array.

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Project description:Cryptococcus neoformans is a ubiquitous environmental fungus that can also cause life-threatening infections in immunocompromised individuals. As a competent pathogen, Cryptococcus needs to reprogram its metabolism to adapt the drastic differences between environmental niches and host niches. A well-curated genome-scale metabolic model (GEM) is a powerful tool to facilitate the investigation of the metabolic resilience of an organism Here we reconstructed and validated iCNG99, a GEM for C. neoformans reference strain H99, and evaluated its predictive performance across 43 growth conditions and gene essentiality benchmarks. The model achieved high confidence essential gene prediction (precision = 0.77) and recapitulated pathways targeted by clinically available antifungals. Integration with transcriptomic and metabolomic data enabled iCNG99 to capture condition-specific metabolic adaptations and to identify candidate vulnerabilities in drug tolerance, revealing metabolic adaptations associated with survival within host conditions and drug susceptibility. Together, iCNG99 provides a systems-level computational platform for investigating C. neoformans metabolism and for prioritizing antifungal vulnerabilities.

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Inositol regulation with Cryptococcus neoformans JEC21 70-mer whole genome array

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.

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Project description:The opportunistic fungal pathogen Cryptococcus neoformans faces a wide range of environmental pH within the host, and adaptation to different pH conditions plays a critical role in their survival and pathogenesis. In the current study, how environmental pH influences antifungal susceptibility and iron uptake in C. neoformans was investigated. We found that acidic pH conditions significantly reduced antifungal susceptibility of C. neoformans to fluconazole. Moreover, our study revealed that iron acquisition in C. neoformans at acidic pH is independent of the high-affinity iron uptake system, and leads to increase of intracellular iron accumulation, increased ergosterol and heme levels, which may contribute to reduced fluconazole susceptibility of the fungus. Transcriptome analysis further elucidated the molecular mechanisms underlying the pH-dependent shift of iron uptake and antifungal susceptibility of C. neoformans. Our findings highlight the importance of environmental pH in physiology and pathogenesis of C. neoformans and provide insights into developing novel treatment for cryptococcosis.

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