Cryptococcus neoformans
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PROVIDER: PRJNA131915 | ENA |
REPOSITORIES: ENA
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Project description:Cryptococcus neoformans lab strain H99 was exposed to fluconazole. Adaptors which obtained tolerance to fluconazole were sequenced
2021-03-13 | E-MTAB-10177 | biostudies-arrayexpress
Project description:Fluconazole (FLC), a triazole antifungal drug, is widely used for the maintenance therapy of cryptococcal meningoencephalitis, the most common opportunistic infection in AIDS patients, but this usage predisposes to the appearance of FLC resistance, especially in patients with no or limited access to highly active antiretroviral therapy. We used microarray analysis to examine changes in the gene expression profile of C. neoformans reference strain H99 (serotype A) following exposure to FLC in order to study the adaptive cellular responses to drug stress. Simultaneous analysis of over 6,823 C. neoformans gene transcript levels revealed that 476 genes were responsive to FLC. Up-regulated expression was observed, as expected, for genes involved in the ergosterol biosynthesis, including ERG13, ERG1, ERG7, ERG25, ERG2, ERG3, ERG5, and that encoding the azole target, ERG11, but also for the gene SRE1, that encodes a well-known regulator of sterol homeostasis in C. neoformans. In addition, several genes such as those involved in a wide variety of important cellular processes (i.e., lipid and fatty acid metabolism, cell wall maintenance, stress, virulence, etc.), were found to be up-regulated in response to fluconazole treatment. Some of these genes may represent potential therapeutic targets to be exploited in anticryptococcal therapy. Conversely, expression of AFR1, the major transporter of azoles in C. neoformans, was shown to be not affected by exposure to FLC, thus suggesting a minor involvement in the C. neoformans short-term adaptation to the azole drug. We studied the transient response of C. neoformans to fluconazole by analyzing differences in gene expression prior to and after exposure of strain H99. Three biological replicates were performed for each condition (FLC-exposed and -not exposed (controls)). The cells were exposed to 10 µg of FLC/ml (1/2 x MIC) or distilled water (controls) for one doubling time (90 min).
2010-11-15 | E-GEOD-24927 | biostudies-arrayexpress
Project description:Fluconazole (FLC), a triazole antifungal drug, is widely used for the maintenance therapy of cryptococcal meningoencephalitis, the most common opportunistic infection in AIDS patients, but this usage predisposes to the appearance of FLC resistance, especially in patients with no or limited access to highly active antiretroviral therapy. We used microarray analysis to examine changes in the gene expression profile of C. neoformans reference strain H99 (serotype A) following exposure to FLC in order to study the adaptive cellular responses to drug stress. Simultaneous analysis of over 6,823 C. neoformans gene transcript levels revealed that 476 genes were responsive to FLC. Up-regulated expression was observed, as expected, for genes involved in the ergosterol biosynthesis, including ERG13, ERG1, ERG7, ERG25, ERG2, ERG3, ERG5, and that encoding the azole target, ERG11, but also for the gene SRE1, that encodes a well-known regulator of sterol homeostasis in C. neoformans. In addition, several genes such as those involved in a wide variety of important cellular processes (i.e., lipid and fatty acid metabolism, cell wall maintenance, stress, virulence, etc.), were found to be up-regulated in response to fluconazole treatment. Some of these genes may represent potential therapeutic targets to be exploited in anticryptococcal therapy. Conversely, expression of AFR1, the major transporter of azoles in C. neoformans, was shown to be not affected by exposure to FLC, thus suggesting a minor involvement in the C. neoformans short-term adaptation to the azole drug.
2010-11-15 | GSE24927 | GEO
Project description:Transcriptome profiling of wild type and cfo1 mutant with fluconazole treatment in Cryptococcus neoformans var. grubii H99 Purpose: The goals of this study are to compare cfo1 mutant transcriptome profiling (RNA-seq) to wild-type with or without fluconazole treatment in Cryptococcus neoformans var. grubii H99. Methods: mRNA profiles of wild-type and cfo1 mutant with or without fluconazole treatment 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: Compared to wild-type, a number of genes were differentially expressed in the cfo1 mutant, especially genes involved in iron homeostasis and transport, ergosterol biosynthesis, mitochondrial function and respiration. Conclusions: Our data suggested reduced expression of the genes in the respiratory chain is the main reason for altered antifungal sensitivity of the cfo1 mutant. The results of our study revealed that iron uptake plays a key role in fluconazole sensitivity of C. neoformans.
2013-05-31 | GSE37875 | GEO
Project description:The cAMP-pathway plays a central role in regulation of growth, differentiation, and virulence of human pathogenic fungi, including Cryptococcus neoformans. Three major upstream signaling regulators of the adenylyl cyclase (Cac1), Ras, Aca1 (Adenylyl cyclase-associated protein 1) and G-alpha subunit protein (Gpa1), have been identified to control the cAMP-pathway in C. neoformans, but their functional relationship remains elusive. Here we performed genome-wide transcriptome analysis with C. neoformans ras1, gpa1, cac1, aca1, and pka1 pka2 mutants by DNA microarray. The aca1, gpa1, cac1, and pka1 pka2 mutants displayed similar transcriptome patterns to each other whereas the ras1 mutant exhibited distinctive transcriptome patterns compared to WT and the cAMP mutants. Interestingly, a number of environmental stress response genes are differentially modulated in the ras1 and cAMP mutants. In fact, the Ras1-signaling pathway was found to be involved in osmotic and genotoxic stress response, and maintenance of cell wall integrity via the Cdc24-dependent signaling pathway. Through this microarray analysis, we have identified a number of cAMP-dependent genes, including GRE2, HSP12, ENA1, TCO2, PKP2, CAT1, in C. neoformans. Notably, a majority of ergosterol biosynthesis genes were found to be upregulated in the cAMP mutants. Interestingly, the gpa1, cac1, and pka1 mutants, but not the aca1 and pka2 mutants were hypersensitive to amphotericin B, but resistant to fluconazole. In conclusion, we demonstrated in this study that the Ras1- and cAMP-signaling pathways are involved in stress response and sterol biosynthesis of C. neoformans. There are more than 95% of genome homology between JEC21 and H99. Therefore 100 slides of JEC21 (cryptococcus neoformans var. neoformans serotype D) 70-mer oligo are used in this analysis, 3 biological replicate experiments are performed, total RNAs are extracted with 6 strains from H99 (H99 Wild type strain (Cryptococcus neoformans var. grubii serotype A), ras1Î, aca1Î, gpa1Î, cac1Î, pka1Îpka2Î), We use the mixed all of total RNAs from this experiment as a control RNA. We use Cy5 as Sample dye and Cy3 as a control dye. several sample are dye swaped.
2010-05-22 | E-GEOD-17338 | biostudies-arrayexpress
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.
2024-03-06 | GSE260902 | GEO
Project description:Fungal disease impacts the lives of almost a billion people across the globe. The opportunistic human fungal pathogen, Cryptococcus neoformans, causes cryptococcal meningitis in immunocompromised individuals with high fatality rates in response to limited treatment options. Moreover, the emergence of azole-resistant isolates in the clinic following prolonged treatment regimes, environmental fungicide exposure, and fungal evolution, threatens the outcome of current therapeutic options, endangering the survival of infected individuals. By quantitatively characterizing the proteomes of fluconazole-susceptible and -resistant C. neoformans strains using state-of-the-art tandem mass spectrometry, we defined ClpX, an ATP-dependent unfoldase, as a target to overcome resistance. We discovered that disruption of ClpX through deletion or inhibition re-introduces fluconazole susceptibility into the resistant strains, rendering treatment effective once again. We further explored the mechanism of susceptibility and determined interruption to heme biosynthesis and ergosterol production associated with ClpX. Our results contribute to the understanding of novel mechanisms driving fluconazole resistance and provide support for targeting proteins as a therapeutic strategy to combat resistance.
2025-07-04 | PXD052366 | Pride
Project description:In Cryptococcus neoformans, H99 is the wild type. TJ1843 is a strains with segmental disomy of chromosome 11, which is derived from H99. In this study, approximately 1 million cells of TJ1843 were spread on YPD plate supplemented with 32 ug/ml fluconazole. Randomly 27 adaptors (TJ3305 and TJ3331) were chosen. These adaptors were sequenced.
2023-08-17 | E-MTAB-12540 | biostudies-arrayexpress
Project description:Transcriptome profiling of wild type and cfo1 mutant with fluconazole treatment in Cryptococcus neoformans var. grubii H99 Purpose: The goals of this study are to compare cfo1 mutant transcriptome profiling (RNA-seq) to wild-type with or without fluconazole treatment in Cryptococcus neoformans var. grubii H99. Methods: mRNA profiles of wild-type and cfo1 mutant with or without fluconazole treatment 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: Compared to wild-type, a number of genes were differentially expressed in the cfo1 mutant, especially genes involved in iron homeostasis and transport, ergosterol biosynthesis, mitochondrial function and respiration. Conclusions: Our data suggested reduced expression of the genes in the respiratory chain is the main reason for altered antifungal sensitivity of the cfo1 mutant. The results of our study revealed that iron uptake plays a key role in fluconazole sensitivity of C. neoformans. mRNA profiles of wild-type and cfo1 mutant with fluconazole treatment were generated by RNA-Seq, using Illumina GAIIx.
2013-05-31 | E-GEOD-37875 | biostudies-arrayexpress
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