Expression profiles of circRNAs in peripherial blood mononuclear cells from cryptococcal meningitis and healthy individuals.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE159601 | GEO | 2020/12/07
REPOSITORIES: GEO
Similar Datasets
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
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:Single-end reads of serial isolates from cryptococcal meningitis cases
| PRJEB28390 | ENA
Project description:Quantitative proteomics of cryptococcal meningitis brain tissues and control brain tissues was carried out to study the host factors that are activated and differentially regulated in response to infection. Proteins isolated from infected brain tissues were subjected to trypsin digestion and then labeled using 4-plex iTRAQ labels. iTRAQ labeled peptides were subjected to fractionation by SCX. All the fractions were analyzed on the high resolution Orbitrap Velos mass spectrometer.
2015-07-22 | PXD000458 | Pride
Project description:Ubiquitination is a reversible protein modification involved in various cellular processes in eukaryotic cells. Deubiquitinating enzymes, the proteins responsible for the removal of ubiquitin, act as essential regulators to maintain ubiquitin homeostasis and to exquisitely regulate protein degradation via the ubiquitination pathway. Cryptococcus neoformans is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily within the immunocompromised population. In order to understand the possible influence deubiquitinating enzymes have on growth and virulence of the model pathogenic yeast Cryptococcus neoformans, we generated deletion mutants of 7 putative deubiquitinase genes. Compared to other deubiquitinating enzyme mutants, a ubp5∆ mutant exhibited severely attenuated virulence and many distinct phenotypes, including decreased capsule formation, hypomelanization, defective sporulation, and elevated sensitivity to several external stressors (such as high temperature, oxidative and nitrosative stresses, high salts, and antifungal agents). Ubp5 appears to be the major deubiquitinating enzyme in C. neoformans for maintaining a pool of free ubiquitin for stress responses, supports the evolutionary divergence of Cryptococcus sp. from the model yeast S. cerevisiae, and provides an important paradigm for understanding the potential role of deubiquitination in virulence by other pathogenic fungi. In addition, other putative deubiquitinase mutants (doa4∆ and ubp13∆) exhibit similar phenotypes to the ubp5∆ mutant, illustrating possible functional overlap among deubiquitinating enzymes in C. neoformans. Certain functioning deubiquitinating enzymes are essential for the virulence composite of C. neoformans and provide an additional yeast survival and propagation advantage in the host. New Zealand White rabbits were inoculated with WT strain H99 and harvested by intracisternal spinal tap on days 1, 3, 4, and 7. For the human sample, RNA was extracted from CSF obtained from a de-identified patient with cryptococcal meningitis.
2012-04-10 | E-GEOD-36183 | biostudies-arrayexpress
Project description:Expression profiles of circRNAs in peripherial blood mononuclear cells from cryptococcal meningitis and healthy individuals.
| PRJNA669854 | ENA
Project description:Bacterial persisters, a subpopulation of genetically susceptible cells that are normally dormant and tolerant to bactericides, have been studied extensively because of their clinical importance. In comparison, much less is known about the determinants underlying fungicide-tolerant fungal persister formation in vivo. Here, we report that during mouse lung infection, Cryptococcus neoformans forms persisters that are highly tolerant to amphotericin B (AmB), the standard of care for treating cryptococcosis. By exploring stationary-phase indicator molecules and developing single-cell tracking strategies, we show that in the lung, AmB persisters are enriched in cryptococcal cells that abundantly produce stationary-phase molecules. The antioxidant ergothioneine plays a specific and key role in AmB persistence, which is conserved in phylogenetically distant fungi. Furthermore, the antidepressant sertraline shows potent activity specifically against cryptococcal AmB persisters. Our results provide evidence for and the determinant of AmB-tolerant persister formation in pulmonary cryptococcosis, which has potential clinical significance.
2024-01-08 | GSE233619 | GEO
Project description:Cryptococcus neoformans is a fungal pathogen responsible for an increased mortality among immunocompromised individuals. Long antifungal therapies to treat cryptococcal infections have compounded the occurrence of resistant strains that threaten the efficacy of current treatments. In this senseDue to resistance mechanisms, discovery of compounds that inhibit virulence factors, rather than kill the fungus, have emerged as potential new strategies to combat infection and reduce the rate of resistance due to lower selective pressure. Invertebrates rely solely on an effective innate immune system to prevent infections, provide providing a potential one health approach for discovery of novel antifungal and antibacterial compounds. Here, we demonstrate a differentiated extraction of proteins from three mollusks (freshwater and terrestrial) and evaluate extract their effects against the growth and virulence factor production (thermotolerance, melanin, capsule, and biofilm) in C. neoformans. We show that clarified extracts of Planorbella pilsbryi have a fungicidal effect on cryptococcal cells in a comparable way to Fluconazolefluconazole. Similarly, crude and clarifiedall extracts of Cipangopaludina chinensis not only affects cryptococcal thermotolerance but also impairs biofilm and capsule production. In addition, incubation of C. neoformans with clarified extracts of Cepaea nemoralis extracts reduced capsule production. Using inhibitory activity of extracts against peptidases related with virulence factors and Quantitative quantitative proteomics arose distinct proteome signatures for each extract and proposed proteins driving the observed anti-virulence properties. Overall, this work demonstratesproves the potential of compounds derived from natural sources to inhibit virulence factor production in a clinically important fungal pathogen.
2023-03-06 | PXD038987 | Pride
Project description:In eukaryotes, inositol polyphosphates perform essential metabolic and signaling functions. Using human fungal pathogen Cryptococcus neoformans as a model, we created mutants in three inositol polyphosphates kinases: Arg1, Ipk1 and Kcs1. Each of the mutants produces a unique repertoire of inositol polyphosphates, different from the wild type strain. Comparative phenotypic and transcriptome analyses of wild type and mutant strains indicates that inositol polyphosphate PP-IP5 (IP7) is the key regulator of gene expression, fitness and virulence in C. neoformans.
2016-03-03 | GSE78824 | GEO
Project description:to identify transcriptomic biomarker pathways in peripheral blood that are associated with or predict the development of death or fatal C-IRIS among patients with CM who were enrolled in the Cryptococcal Optimal ART Timing (COAT) Trial.
2021-03-01 | GSE162914 | GEO