Brain glucose induces tolerance of Cryptococcus neoformans to amphotericin B during meningitis
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ABSTRACT:
PROVIDER: PRJNA780908 | ENA |
REPOSITORIES: ENA
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Project description:In bacteria, antibiotic tolerance, the ability of a susceptible population to survive high doses of cidal drugs, has been shown to compromise therapeutic outcomes. In comparison, whether fungicide tolerance can be induced by host-derived factors during fungal diseases remains unproven. Here, through a systematic evaluation of metabolite-drug-fungal interactions in the leading fungal meningitis pathogen, Cryptococcus neoformans, we found that glucose, on which the brain depends for fuel, induces fungal tolerance to amphotericin B (AmB) in mouse brain tissue and patient cerebrospinal fluid via the fungal glucose repression activator Mig1. To explore the mechanisms underlying glucose-dependent AmB tolerance mediated by Mig1, we used time-series RNA-seq to evaluate dynamic gene expression in wildtype and mig1Δ fungi after exposure to AmB under both drug-tolerant (glucose) or drug-sensitive (galactose) conditions.
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Project description:Cryptococcus neoformans strain H99 was exposed to 3μg/ml amphotericin B. Among the amphotericin B-tolerant adaptors, transcriptomes of four adaptors (TJ1844, TJ1849, TJ1852, TH1854) were analyzed and compared to wild type strain H99.
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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.
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2023-05-11 | E-MTAB-12493 | biostudies-arrayexpress
Project description:Log phase of Cryptococcus neoformans strain H99 was exposed to amphotericin B (1.5μg/ml) or vehicle (control) for 3h. Transcriptome of drug treated cells were compared to no treatment cells.
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Project description:Cryptococcus neoformans strain TJ1854 derived amphotericin B adaptors
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Project description:In this study, H99 is a wild type Cryptococcus neoformans strain. TJ1854 is a chromosome 4 disomy strain derived from H99. Approximately 1 million cells of TJ1854 were spread on YPD plate supplemented with 6ug/ml amphtericin B. Randomlyh 27 adaptors (TJ2487-TJ2513) were chosen. These adaptors were sequenced.
2023-03-15 | E-MTAB-12480 | 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
Project description:Cryptococcus neoformans is a major cause of fungal meningitis in immunocompromised individuals worldwide. Studies have categorized the transcriptome of Cryptococcus under various stresses, such as temperature, nitric oxide, iron, antifungal drugs and macrophages. However, an accurate and comprehensive transcriptome profiling of C. neoformans in the human host may allow an even better understanding of its survival and disease production. In this study, we isolated RNA from yeast cells taken directly from CSF of two individuals with cryptococcal meningitis. RNA-Seq was used to generate and compare transcriptional profiles from those yeast cells exposed to three environmental conditions. Under same conditions, similar expression patterns were found between the two strains with different genotypes. Yeast cells from in vivo CSF appear to be more metabolically active compared to those exposed to ex vivo CSF. Moreover, genes that were identified as significantly up-regulated in both ex vivo CSF and in vivo CSF conditions compared with growth in YPD appear to be important for the virulence of Cryptococcus. In the central nervous system, differentially expressed genes, single nucleotide variants and novel genes between strains were identified to emphasize that strains have consensus expression patterns but they do have their unique features. Genes with transporter functions were found to be enriched in the regulated transcripts demonstrating this important function of yeasts under host stress. These findings provide the platform for further interrogation into how this yeast survives in humans to provide identification of possible antifungal target(s) and/or genetic signatures to predict outcome.
2013-11-10 | GSE51573 | GEO
Project description:Cryptococcus neoformans is a major cause of fungal meningitis in immunocompromised individuals worldwide. Studies have categorized the transcriptome of Cryptococcus under various stresses, such as temperature, nitric oxide, iron, antifungal drugs and macrophages. However, an accurate and comprehensive transcriptome profiling of C. neoformans in the human host may allow an even better understanding of its survival and disease production. In this study, we isolated RNA from yeast cells taken directly from CSF of two individuals with cryptococcal meningitis. RNA-Seq was used to generate and compare transcriptional profiles from those yeast cells exposed to three environmental conditions. Under same conditions, similar expression patterns were found between the two strains with different genotypes. Yeast cells from in vivo CSF appear to be more metabolically active compared to those exposed to ex vivo CSF. Moreover, genes that were identified as significantly up-regulated in both ex vivo CSF and in vivo CSF conditions compared with growth in YPD appear to be important for the virulence of Cryptococcus. In the central nervous system, differentially expressed genes, single nucleotide variants and novel genes between strains were identified to emphasize that strains have consensus expression patterns but they do have their unique features. Genes with transporter functions were found to be enriched in the regulated transcripts demonstrating this important function of yeasts under host stress. These findings provide the platform for further interrogation into how this yeast survives in humans to provide identification of possible antifungal target(s) and/or genetic signatures to predict outcome. Examination of mRNA expression levels under three different conditions of two different strains with different genotypes
2013-11-10 | E-GEOD-51573 | biostudies-arrayexpress