Aspergillus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA802395 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR17844320_1.fastq.gz | Fastqsanger.gz | |||
| SRR17844320_2.fastq.gz | Fastqsanger.gz | |||
| SRR17844321_1.fastq.gz | Fastqsanger.gz | |||
| SRR17844321_2.fastq.gz | Fastqsanger.gz |
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Project description:The Aspergillus fumigatus sterol regulatory element binding protein (SREBP) SrbA belongs to the basic Helix-Loop-Helix (bHLH) family of transcription factors and is crucial for antifungal drug resistance and virulence. The latter phenotype is especially striking, as loss of SrbA results in complete loss of virulence in murine models of invasive pulmonary aspergillosis (IPA). How fungal SREBPs mediate fungal virulence is unknown, though it has been suggested that lack of growth in hypoxic conditions accounts for the attenuated virulence. To further understand the role of SrbA in fungal infection site pathobiology, chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) was used to identify genes under direct SrbA transcriptional regulation in hypoxia. These results confirmed the direct regulation of ergosterol biosynthesis and iron uptake by SrbA in hypoxia and revealed new roles for SrbA in nitrate assimilation and heme biosynthesis. Moreover, functional characterization of an SrbA target gene with sequence similarity to SrbA identified a new transcriptional regulator of the fungal hypoxia response and virulence, SrbB. SrbB co-regulates genes involved in heme biosynthesis and demethylation of C4 sterols with SrbA in hypoxic conditions. However, SrbB also has regulatory functions independent of SrbA including regulation of carbohydrate metabolism. Loss of SrbB markedly attenuates A. fumigatus virulence, and loss of both SREBPs further reduces in vivo fungal growth. These data suggest that both A. fumigatus SREBPs are critical for hypoxia adaptation and virulence and reveals new insights into SREBPM-bM-^@M-^Ys complex role in infection site adaptation and fungal virulence. 4 hour and 12 hour ChIP experiments were completed. Input control samples for each set were collected.
2014-10-03 | E-GEOD-61974 | biostudies-arrayexpress
Project description:The Aspergillus fumigatus sterol regulatory element binding protein (SREBP) SrbA belongs to the basic Helix-Loop-Helix (bHLH) family of transcription factors and is crucial for antifungal drug resistance and virulence. The latter phenotype is especially striking, as loss of SrbA results in complete loss of virulence in murine models of invasive pulmonary aspergillosis (IPA). How fungal SREBPs mediate fungal virulence is unknown, though it has been suggested that lack of growth in hypoxic conditions accounts for the attenuated virulence. To further understand the role of SrbA in fungal infection site pathobiology, chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) was used to identify genes under direct SrbA transcriptional regulation in hypoxia. These results confirmed the direct regulation of ergosterol biosynthesis and iron uptake by SrbA in hypoxia and revealed new roles for SrbA in nitrate assimilation and heme biosynthesis. Moreover, functional characterization of an SrbA target gene with sequence similarity to SrbA identified a new transcriptional regulator of the fungal hypoxia response and virulence, SrbB. SrbB co-regulates genes involved in heme biosynthesis and demethylation of C4 sterols with SrbA in hypoxic conditions. However, SrbB also has regulatory functions independent of SrbA including regulation of carbohydrate metabolism. Loss of SrbB markedly attenuates A. fumigatus virulence, and loss of both SREBPs further reduces in vivo fungal growth. These data suggest that both A. fumigatus SREBPs are critical for hypoxia adaptation and virulence and reveals new insights into SREBP’s complex role in infection site adaptation and fungal virulence.
2014-10-03 | GSE61974 | GEO
Project description:As a sister genus to Taxus, Pseudotaxus holds significant importance for studying the origin and evolution of the taxane biosynthesis pathway. However, the reference genome of P. chienii, the sole species of Pseudotaxus, is not yet available. We have completed a chromosome-level genome assembly of P. chienii, with a total length of 15.6 Gb. P. chienii possesses only a partial pathway for Taxol biosynthesis, which terminates before the enzyme taxane 2α-O-benzoyl transferase (TBT), a crucial enzyme responsible for the production of 10-deacetylbaccatin III. With the emergence of the Taxus genus, the limitation posed by TBT is overcome, allowing for the extension of the existing taxane biosynthesis pathway into a complete Taxol biosynthesis pathway. Protein structure analysis revealed that the structure of metal ion catalysis sites in taxadiene synthase (TS) is conserved across the Pseudotaxus and Taxus genera, providing potential sites for enhancing TS activity through enzyme engineering. This comparative genomic analysis contributes to our understanding of the origin and evolution of taxane biosynthesis within the Taxaceae family.
2025-01-27 | GSE288094 | GEO
Project description:Inhalation of conidia of the opportunistic mold Aspergillus fumigatus by immunocompromised hosts can lead to invasive pulmonary disease. Inhaled conidia that escape immune defenses germinate to form filamentous hyphae that invade lung tissues. Conidiation rarely occurs during invasive infection of the human host, allowing the bulk of fungal energy to be directed towards vegetative growth. We hypothesized that forced induction of conidiation during infection can suppress A. fumigatus vegetative growth, impairing the ability of this organism to cause disease. To study the effects of conidiation pathway dysregulation on A. fumigatus virulence, a key transcriptional regulator of conidiation (brlA) was expressed under the control of a doxycycline-inducible promoter. Time- and dose-dependent brlA overexpression was observed in response to doxycycline both in vitro and in vivo. Exposure of the inducible brlA overexpression strain to low doses of doxycycline under vegetative growth conditions in vitro induced conidiation, while high doses arrested growth. Overexpression of brlA attenuated A. fumigatus virulence in both an invertebrate and mouse model of invasive aspergillosis. RNA sequencing studies and phenotypic analysis revealed that brlA-overexpression results in altered cell signaling, amino acid and carbohydrate metabolism, including a marked up-regulation of trehalose biosynthesis and a downregulation in the biosynthesis of the polysaccharide virulence factor galactosaminogalactan. This proof-of-concept study demonstrates that activation of the conidiation pathway in A. fumigatus can reduce virulence and suggests that brlA-inducing small molecules may hold promise as a new class of therapeutics for A. fumigatus infection.
2020-01-15 | GSE143601 | GEO
Project description:Aflatoxins are toxic and carcinogenic polyketide metabolites produced by fungal species, including Aspergillus flavus and A. parasiticus. The biosynthesis of aflatoxins is modulated by many environmental factors, including the availability of a carbon source. The gene expression profile of A. parasiticus was evaluated during a shift from a medium with low concentration of simple sugars, Yeast Extract (YE), to a similar medium with sucrose, Yeast Extract Sucrose (YES). Total RNA and aflatoxins (B1, B2, G1, and G2) were quantified from fungal mycelia harvested pre- and post-shifting. When compared to YE media, YES caused temporary reduction of the aflatoxin levels detected at 3 hours post-shifting and they remained low well past 12 hours post-shift. Aflatoxin levels did not exceed the levels in YE until 24 hrs post shift, at which time point a 10-fold increase was observed over YE. Microarray analysis comparing the RNA samples from the 48 hr YE culture to the YES samples identified a total of 2120 genes that were expressed across all experiments, including most of the aflatoxin biosynthesis genes. One-way Analysis of Variance (ANOVA) identified 56 genes that were expressed with significant variation across all time points. Three genes responsible for converting norsolorinic acid to averantin were identified among these significantly expressed genes. The potential role of these genes involvement in the regulation of aflatoxin biosynthesis is discussed. Keywords: time course, media shift, Aspergillus, aflatoxin
2007-10-01 | GSE8038 | GEO
Project description:The RNA interference (RNAi) pathway has evolved numerous functionalities in eukaryotes, with many on display in Kingdom Fungi. RNAi can regulate gene expression, facilitate drug resistance, or even be altogether lost to improve virulence potential in some fungal pathogens. In the WHO fungal priority pathogen, Aspergillus fumigatus, the RNAi system is known to be intact and functional. To extend our limited understanding of A. fumigatus RNAi, we performed a multi-condition sRNA-seq analysis comparing expression of several RNAi double knockout mutants with the wild-type strain in conidia and mycelium grown for 24 or 48 hours.
2024-05-25 | GSE267454 | GEO
Project description:Gene expression microarray was performed to assess the global changes coupled to targeted validation of proteomic profiling to reveal the broad anticancer activities of the immunosuppressive drug Mycophenolic acid (MPA) and elucidate the molecular mechanisms underlying these activities. We conducted gene expression microarray experiments on AGS cancers cells treated with Mycophenolic acid (MPA). A concentration of 2ug/ml was selected to treat AGS cells and the treated cells were harvested at 0, 12, 24, 48 and 72 hours of culture with the drug. Gene expression analyses were carried out using Illumina Human 12 Beadchips.
2013-10-28 | E-GEOD-46671 | biostudies-arrayexpress