Cryptococcus neoformans H99
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ABSTRACT:
PROVIDER: PRJNA239378 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A 13-(4-isopropylbenzyl)berberine derivative (named KR-72) was synthesized and examined for antifungal activities against various human pathogenic fungi. The synthesized compound exhibited remarkably enhanced antifungal activity than berberine and berberrubine. Regardless of the potent antifungal activity of KR-72, its mode of action and the physiological impacts of the drug on fungal metabolism remain elusive. In this study, we performed the DNA microarray-based transcriptome analysis to identify KR-72 responsive genes and employed reverse genetics approaches to characterize their functions in Cryptococcus neoformans, which causes fatal meningoencephalitis in humans. First, KR-72 treatment altered in remodeling of transcriptome profiles in C. neoformans. Genes involved in translation and transcription were mostly upregulated, while those involved in cytoskeleton, intracellular trafficking, lipid and carbohydrate metabolism and energy production were downregulated. Supporting this, KR-72 has a strong synergistic effect with a calcineurin inhibitor FK506, while it has an antagonistic effect with polyene drug. Finally, KR-72 treatment promoted expression of ECM16, NOP14, HSP10, and MGE1, which we proved to be essential for the growth of C. neoformans. Among them, KR-72 mediated induction of MGE1 also appeared to hamper the viability of C. neoformans, potentially through impaired cell cycle or DNA repair system. This study will proposed mode of action for KR-72.
2014-02-26 | GSE55337 | GEO
Project description:A 13-(4-isopropylbenzyl)berberine derivative (named KR-72) was synthesized and examined for antifungal activities against various human pathogenic fungi. The synthesized compound exhibited remarkably enhanced antifungal activity than berberine and berberrubine. Regardless of the potent antifungal activity of KR-72, its mode of action and the physiological impacts of the drug on fungal metabolism remain elusive. In this study, we performed the DNA microarray-based transcriptome analysis to identify KR-72 responsive genes and employed reverse genetics approaches to characterize their functions in Cryptococcus neoformans, which causes fatal meningoencephalitis in humans. First, KR-72 treatment altered in remodeling of transcriptome profiles in C. neoformans. Genes involved in translation and transcription were mostly upregulated, while those involved in cytoskeleton, intracellular trafficking, lipid and carbohydrate metabolism and energy production were downregulated. Supporting this, KR-72 has a strong synergistic effect with a calcineurin inhibitor FK506, while it has an antagonistic effect with polyene drug. Finally, KR-72 treatment promoted expression of ECM16, NOP14, HSP10, and MGE1, which we proved to be essential for the growth of C. neoformans. Among them, KR-72 mediated induction of MGE1 also appeared to hamper the viability of C. neoformans, potentially through impaired cell cycle or DNA repair system. This study will proposed mode of action for KR-72. The six slides of Cryptococcus_neoformans 3X20K are used in this analysis, 3 biological replicate experiments are performed, total RNAs are extracted under 2 conditions (with or without treatment of KR-72 with H99 (H99 Wild type strain (Cryptococcus neoformans var. grubii serotype A). We use the KR-72 non-treated RNAs from this experiment as a control RNA. We use Cy5 as Sample dye and Cy3 as a control dye.
2014-02-26 | E-GEOD-55337 | biostudies-arrayexpress
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
Project description:Global transcriptome analysis of eukaryotic genes affected by Gromwell extract
| PRJNA185756 | ENA
Project description:A defect in iron uptake enhances the susceptibility of Cryptococcus neoformans to azole antifungal drugs.
| PRJNA164705 | ENA
Project description:Cryptococcus neoformans is a human fungal pathogen that is the causative agent of cryptococcosis and fatal meningitis in immuno-compromised hosts. Recent studies suggest that copper (Cu) acquisition plays an important role in C. neoformans virulence, as mutants that lack Cuf1, which activates the Ctr4 high affinity Cu importer, are hypo-virulent in mouse models. To understand the constellation of Cu-responsive genes in C. neoformans and how their expression might contribute to virulence, we determined the transcript profile of C. neoformans in response to elevated Cu or Cu deficiency. We identified two metallothionein genes (CMT1 and CMT2), encoding cysteine-rich Cu binding and detoxifying proteins, whose expression is dramatically elevated in response to excess Cu. We identified a new C. neoformans Cu transporter, CnCtr1, that is induced by Cu deficiency and is distinct from CnCtr4 and which shows significant phylogenetic relationship to Ctr1 from other fungi. Surprisingly, in contrast to other fungi, we found that induction of both CnCTR1 and CnCTR4 expression under Cu limitation, and CMT1 and CMT2 in response to Cu excess, are dependent on the CnCuf1 Cu metalloregulatory transcription factor. These studies set the stage for the evaluation of the specific Cuf1 target genes required for virulence in C. neoformans.
| S-EPMC3718005 | biostudies-literature
Project description:Purpose: The purpose of this study is to define the mechanism of antifungal action of the vanillin derivative, o-vanillin, against Cryptococcus neoformans Methods: mRNA profiles of C. neoformasn cells cultured with or without o-vanillin were generated by RNA-Seq, using Illumina GAIIx. The sequence reads that passed quality filters were mapped to reference genome and the normalized RPKM values were calculated by CLC Genomics Workbench. Results: o-vanillin significantly altered global transcript profiles, induces oxidative stress, and interferes mitochondrial functions in C. neoformans. Conclusions: o-vanillin can be considered as the effective antifungal drug candidate.
2014-10-22 | GSE52645 | GEO
Project description:The infection of Cryptococcus neoformans is acquired through the inhalation of desiccated yeast cells and basidiospores originated from the environment, particularly from bird's droppings and decaying wood. Three environmental strains of C. neoformans originated from bird droppings (H4, S48B and S68B) and C. neoformans reference clinical strain (H99) were used for intranasal infection in C57BL/6 mice. We showed that the H99 strain demonstrated higher virulence compared to H4, S48B and S68B strains. To examine if gene expression contributed to the different degree of virulence among these strains, a genome-wide microarray study was performed to inspect the transcriptomic profiles of all four strains. Our results revealed that out of 7,419 genes (22,257 probes) examined, 65 genes were significantly up-or down-regulated in H99 versus H4, S48B and S68B strains. The up-regulated genes in H99 strain include Hydroxymethylglutaryl-CoA synthase (MVA1), Mitochondrial matrix factor 1 (MMF1), Bud-site-selection protein 8 (BUD8), High affinity glucose transporter 3 (SNF3) and Rho GTPase-activating protein 2 (RGA2). Pathway annotation using DAVID bioinformatics resource showed that metal ion binding and sugar transmembrane transporter activity pathways were highly expressed in the H99 strain. We suggest that the genes and pathways identified may possibly play crucial roles in the fungal pathogenesis.
| S-EPMC4567374 | biostudies-literature
Project description:Purpose: The purpose of this study is to define the mechanism of antifungal action of the vanillin derivative, o-vanillin, against Cryptococcus neoformans Methods: mRNA profiles of C. neoformasn cells cultured with or without o-vanillin were generated by RNA-Seq, using Illumina GAIIx. The sequence reads that passed quality filters were mapped to reference genome and the normalized RPKM values were calculated by CLC Genomics Workbench. Results: o-vanillin significantly altered global transcript profiles, induces oxidative stress, and interferes mitochondrial functions in C. neoformans. Conclusions: o-vanillin can be considered as the effective antifungal drug candidate. mRNA profiles of the cells grown in the presence or absence of o-vanillin were generated by RNA-Seq using Illumina GAIIx.
2014-10-22 | E-GEOD-52645 | biostudies-arrayexpress
Project description:In this study, we designed a novel antifungal agent, PQA-Az-13 that demonstrated antifungal activity against C. auris biofilms. Cellular proteomics indicated that PQA-Az-13 partially or completely inhibited numerous enzymatic proteins in C. auris biofilms, particularly those involved in both amino acid biosynthesis and metabolism processes, as well as in general energy-producing processes. Due to its hydrophobic nature and limited aqueous solubility, PQA-Az-13 was encapsulated in cationic liposomes and characterized by biophysical and spectral techniques. PQA-Az-13 liposomes demonstrated enhanced antifungal activity levels against both C. auris in in vitro biofilms and ex vivo skin colonization models.
2023-12-07 | PXD046911 | Pride