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Cryptococcus neoformans H99

ABSTRACT: A defect in iron uptake enhances the susceptibility of Cryptococcus neoformans to azole antifungal drugs.

PROVIDER: PRJNA164705 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR495425.fastq.gz	Fastqsanger.gz
	SRR495426.fastq.gz	Fastqsanger.gz
	SRR495427.fastq.gz	Fastqsanger.gz
	SRR495428.fastq.gz	Fastqsanger.gz

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Transcriptomics analysis of amphotericin B and lactoferrin drug synergy in Cryptococcus neoformans H99

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.

2019-09-08 | GSE130375 | GEO

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.

2019-06-22 | GSE133125 | GEO

Acidic pH Reduces Fluconazole Susceptibility in Cryptococcus neoformans by Altering Iron Uptake and Enhancing Ergosterol Biosynthesis

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.

2025-03-18 | GSE291861 | GEO

Interplay between acetylation and ubiquitination of Isw1 confers multidrug resistance in Cryptococcus neoformans

Project description:Lysine acetylation and ubiquitination are one of many protein modifications and play a crucial role in the biological regulation of many organisms, but little is known about the relationship between acetylation and ubiquitination few. Here, the Isw1 protein is an important member of the chromatin remodeling complex, and we performed single-protein modification mass spectrometry detection of the C. neoformans Isw1 protein and site mutations for both detected modifications. The data showed that the two modifications of Cryptococcus neoformans Isw1 protein have a balance of each other. Acetylation can maintain protein stability and maintain protein function, while ubiquitination can reduce protein level and maintain Isw1 protein expression. The expression level of Isw1 protein leads to resistance to antifungal drugs. These results reveal the resistance mechanism of Isw1 protein of Cryptococcus neoformans to antifungal drugs.

2022-12-26 | PXD037150 | Pride

Interplay between acetylation and ubiquitination of Isw1 confers multidrug resistance in Cryptococcus neoformans

2023-09-13 | PXD045338 |

The zinc finger protein Mig1 regulates mitochondrial function and azole drug susceptibility in the pathogenic fungus Cryptococcus neoformans

Project description:The opportunistic pathogen Cryptococcus neoformans causes fungal meningoencephalitis in immunocompromised individuals. In previous studies, we found that the Hap complex in this pathogen represses genes encoding mitochondrial respiratory functions and TCA cycle components under low-iron conditions. The orthologous Hap2/3/4/5 complex in Saccharomyces cerevisiae exerts a regulatory influence on mitochondrial functions and Hap4 is subject to glucose repression via the carbon catabolite repressor Mig1. In this study, we explored the regulatory link between a candidate ortholog of the Mig1 protein and the HapX component of the Hap complex in C. neoformans. This analysis revealed repression of MIG1 by HapX and activation of HAPX by Mig1 in low iron conditions, and Mig1 regulation of mitochondrial functions including respiration, tolerance for reactive oxygen species, and expression of genes for iron-consuming and iron-acquisition functions. Consistent with these regulatory functions, a mig1Î mutant had impaired growth on inhibitors of mitochondrial respiration and ROS inducers. Furthermore, deletion of MIG1 provoked a dysregulation in nutrient sensing via the TOR pathway and impacted the pathway for cell wall remodeling. Importantly, loss of Mig1 increased susceptibility to fluconazole thus further establishing a link between azole antifungal drugs and mitochondrial function. Mig1 and HapX were also required together for survival in macrophages, but Mig1 alone had a minimal impact on virulence in mice. Overall, these studies provide novel insights into a HapX/Mig1 regulatory network and reinforce an association between mitochondrial dysfunction and drug susceptibility that may provide new targets for the development of antifungal drugs. In this study, transcription profiles of WT and mig1D mutant strains of Cryptococcus neoformans were compared in a dye-swap experiment following 6hr exposure to Low Iron Medium (LIM) or LIM + 100mM FeCl3.

2015-12-17 | E-GEOD-76063 | biostudies-arrayexpress

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Project description:Cryptococcus neoformans H99 Raw sequence reads

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Project description:A defect in ATP-citrate lyase links acetyl-CoA production, virulence factor elaboration and virulence in Cryptococcus neoformans

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Overexpression of the transcription factor GAT201 in Cryptococcus neoformans var. grubii (serotype A, H99)

Project description:Comparison of transcriptional profiles of WT Cryptococcus neoformans (H99) and strain CM126 (pRPL2b-GAT201) which overexpresses the transcription factor GAT201 using a ribosomal protein promoter Keywords: Genetic modification

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Cryptococcus neoformans H99

Project description:Cryptococcus neoformans H99 Transcriptome or Gene expression

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