Histoplasma capsulatum
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ABSTRACT:
PROVIDER: PRJNA121845 | ENA |
REPOSITORIES: ENA
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Project description:The objective of this experiment is to compare gene expression levels of UC26 to wild type G217B.
2010-12-05 | GSE19762 | GEO
Project description:Comparative transcriptomics of infectious spores from the fungal pathogen Histoplasma capsulatum G217B
| PRJNA193984 | ENA
Project description:The fungal pathogen Histoplasma capsulatum is thought to be the most common cause of fungal respiratory infections in immunocompetent humans, yet little is known about its biology. Here we provide the first genome-wide studies to experimentally validate its genome annotation. A functional interrogation of the Histoplasma genome provides critical support for continued investigation into the biology and pathogenesis of H. capsulatum and related fungi. We employed a three-pronged approach to provide a functional annotation for the H. capsulatum G217B strain. First, we probed high-density tiling arrays with labeled cDNAs from cells grown under diverse conditions. These data defined 6,172 transcriptionally active regions (TARs), providing validation of 6,008 gene predictions. Interestingly, 22% of these predictions showed evidence of anti-sense transcription. Additionally, we detected transcription of 264 novel genes not present in the original gene predictions. To further enrich our analysis, we incorporated expression data from whole-genome oligonucleotide microarrays. These expression data included profiling under growth conditions that were not represented in the tiling experiment, and validated an additional 2,249 gene predictions. Finally, we compared the G217B gene predictions to other available fungal genomes, and observed that an additional 254 gene predictions had an ortholog in a different fungal species, suggesting that they represent genuine coding sequences. These analyses yielded a high confidence set of validated gene predictions for H. capsulatum. The transcript sets resulting from this study are a valuable resource for further experimental characterization of this ubiquitous fungal pathogen. The data is available for interactive exploration at http://histo.ucsf.edu.
2011-08-12 | GSE31155 | GEO
Project description:The fungal pathogen Histoplasma capsulatum is thought to be the most common cause of fungal respiratory infections in immunocompetent humans, yet little is known about its biology. Here we provide the first genome-wide studies to experimentally validate its genome annotation. A functional interrogation of the Histoplasma genome provides critical support for continued investigation into the biology and pathogenesis of H. capsulatum and related fungi. We employed a three-pronged approach to provide a functional annotation for the H. capsulatum G217B strain. First, we probed high-density tiling arrays with labeled cDNAs from cells grown under diverse conditions. These data defined 6,172 transcriptionally active regions (TARs), providing validation of 6,008 gene predictions. Interestingly, 22% of these predictions showed evidence of anti-sense transcription. Additionally, we detected transcription of 264 novel genes not present in the original gene predictions. To further enrich our analysis, we incorporated expression data from whole-genome oligonucleotide microarrays. These expression data included profiling under growth conditions that were not represented in the tiling experiment, and validated an additional 2,249 gene predictions. Finally, we compared the G217B gene predictions to other available fungal genomes, and observed that an additional 254 gene predictions had an ortholog in a different fungal species, suggesting that they represent genuine coding sequences. These analyses yielded a high confidence set of validated gene predictions for H. capsulatum. The transcript sets resulting from this study are a valuable resource for further experimental characterization of this ubiquitous fungal pathogen. The data is available for interactive exploration at http://histo.ucsf.edu. The non-redundant genome sequence of Histoplasma capsulatum G217B was tiled over a set of 93 CombiMatrix arrays, which were then hybridized with labeled cDNA samples from yeast-form (red channel) or mycelial-form (green channel) Histoplasma. Due to low yields from the mycelial samples, only the red channel intensities were analyzed (and the red foreground intensities are, therefore, reported in the VALUE column for each sample). Rather than normalizing intensities across arrays, each probe was evaluated as detected or undetected relative to the negative control intensities on the corresponding array, and the density of detected probes as a function of genome position was used for the remaining analysis.
2011-08-11 | E-GEOD-31155 | biostudies-arrayexpress
Project description:Histoplasma capsulatum is a fungal pathogen that infects both healthy and immunocompromised hosts. In endemic regions, H. capsulatum grows in the soil and causes respiratory and systemic disease when inhaled by humans. An interesting aspect of H. capsulatum biology is that it adopts specialized developmental programs in response to its environment. In the soil, it grows as filamentous chains of cells (mycelia) that produce asexual spores (conidia). When the soil is disrupted, conidia aerosolize and are inhaled by mammalian hosts. Inside a host, conidia germinate into yeast-form cells that colonize immune cells and cause disease. Despite the ability of conidia to initiate infection and disease, they have not been explored on a molecular level. Here we develop methods to purify H. capsulatum conidia and show that these cells germinate into either filaments at room temperature or into yeast-form cells at 37C. Conidia internalized by macrophages germinate into the yeast form and proliferate within the macrophages, ultimately lysing the host cells. Similarly, infection of mice with purified conidia is sufficient to establish infection and yield viable yeast-form cells in vivo. To characterize conidia on a molecular level, we perform whole-genome expression profiling of conidia, yeast, and mycelia from two highly diverged H. capsulatum strains. In parallel, we use homology and protein domain analysis to manually annotate the predicted genes of both strains. Analyses of the resultant data define sets of transcripts that reflect the unique molecular states of H. capsulatum conidia, yeast and mycelia. This series gives the results for the G217B strain.
2013-04-10 | GSE45415 | GEO
Project description:Allergens such as house dust mites (HDM) and papain induce strong Th2 responses, including elevated IL-4, IL-5, and IL-13 and marked eosinophilia in the airways. Histoplasma capsulatum is a dimorphic fungal pathogen that induces a strong Th1 response marked by IFN-? and TNF-? production, leading to rapid clearance in nonimmunocompromised hosts. Th1 responses are generally dominant and overwhelm the Th2 response when stimuli for both are present, although there are instances when Th2 stimuli downregulate a Th1 response. We determined if the Th2 response to allergens prevents the host from mounting a Th1 response to H. capsulatum in vivo. C57BL/6 mice exposed to HDM or papain and infected with H. capsulatum exhibited a dominant Th2 response early, characterized by enhanced eosinophilia and elevated Th2 cytokines in lungs. These mice manifested exacerbated fungal burdens, suggesting that animals skewed toward a Th2 response by an allergen are less able to clear the H. capsulatum infection despite an intact Th1 response. In contrast, secondary infection is not exacerbated by allergen exposure, indicating that the memory response may suppress the Th2 response to HDM and quickly clear the infection. In conclusion, an in vivo skewing toward Th2 by allergens exacerbates fungal infection, even though there is a concurrent and unimpaired Th1 response to H. capsulatum.
| S-EPMC6246782 | biostudies-literature
Project description:keywords: murine bone marrow-derived macrophages response to Histoplasma capsulatum yeast infection In order to gain a better understanding of the macrophage response to infection with H. capsulatum, an intracellular fungal pathogen, we conducted a microarray timecourse analysis of gene expression in bone marrow-derived macrophages infected with H. capsulatum yeasts. The H. capsulatum gene CBP1 is required for virulence in animals, and is also necessary for macrophage lysis. Cbp1 protein is secreted, thus we hypothesized that it may interfere with macrophage signaling and/or gene expression. To test this, we compared macrophage gene expression profiles following infection with wild-type or cbp1 mutant yeasts. Additionally, we infected with UV-treated yeasts, which are phagocytosed and quickly degraded in the macrophage. Immediately following infection with either live, UV-treated, or cbp1 mutant yeasts, we observed a canonical inflammatory response signature from 1-3 hpi. At later time points following infection, we observe upregulation of several genes, including the pseudo-kinase Tribbles homolog 3, that have been linked to stress response and cell death in other cell types. The expression of these genes is dependent on CBP1, suggesting that this infection regulon may cause or respond to the initiation of a lytic program. Bone marrow-derived macrophages were isolated from 8 week-old female C57BL/6 mice and either mock-infected, or infected with live H. capsulatum yeasts (strain G217B), UV-treated yeasts, or yeasts harboring an insertion in the gene encoding the virulence factor CBP1. At various time points following infection, we isolated macrophage total RNA and subjected to RNA amplification to generate aRNA. aRNAs were hybed to 64 MEEBO arrays.
2010-10-01 | E-GEOD-23378 | biostudies-arrayexpress
Project description:Comparative transcriptomics of infectious spores from the fungal pathogen Histoplasma capsulatum G186AR
| PRJNA193985 | ENA
Project description:N-acetylglucosamine (GlcNAc) Triggers a Rapid, Temperature-Responsive Morphogenetic Program in Thermally Dimorphic Fungi
| PRJNA208854 | ENA
Project description:Genome-wide reprogramming of transcript architecture by temperature specifies the developmental states of the human pathogen Histoplasma [ribosome profiling]
| PRJNA283425 | ENA