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Aspergillus fumigatus transcriptome under normoxia and hypoxia conditions

ABSTRACT: To better understand the effect of hypoxia, RNA-Seq technology was used to profile the Aspergillus fumigatus during adaptation to hypoxia at 12, 24 and 36 h time points.

ORGANISM(S): Aspergillus fumigatus

PROVIDER: GSE30579 | GEO | 2013/03/31

SECONDARY ACCESSION(S): PRJNA144647

REPOSITORIES: GEO

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Aspergillus fumigatus transcriptome under normoxia and hypoxia conditions

Project description:To better understand the effect of hypoxia, RNA-Seq technology was used to profile the Aspergillus fumigatus during adaptation to hypoxia at 12, 24 and 36 h time points. Four samples examined: from the fungus grown under normoxia and hypoxia conditions

2013-03-31 | E-GEOD-30579 | biostudies-arrayexpress

Aspergillus fumigatus Colony Biofilm Morphology Impacts Hypoxia Fitness, Inflammation, and Disease Progression

Project description:We report gene expression differences in Aspergillus fumigatus wild type, hrmA mutant, and overexpression under hypoxia and normoxia conditions

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Comparative genomic hybridization of Aspergillus fumigatus Af71, Aspergillus fumigatus Af294, Aspergillus clavatus, Neosartorya fenneliae and Neosartorya fischeri with Aspergillus fumigatus Af293

Project description:Genomic DNA from five strains, Aspergillus fumigatus Af71, Aspergillus fumigatus Af294, Aspergillus clavatus, Neosartorya fenneliae, and Neosartorya fischeri, were co-hybridized with that of Aspergillus fumigatus Af293 and compared.

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Transcriptome analysis of conidium germination of Aspergillus fumigatus in different growth conditions

Project description:Gene expression level of Aspergillus fumigatus CEA17_ΔakuBKU80 during germination in two different medium

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ChIP-seq analyses of the Aspergillus fumigatus SREBP SrbA

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

ChIP-seq analyses of the Aspergillus fumigatus SREBP SrbA

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.

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Redox proteomic analysis reveals an important role for protein oxidative modifications in hypoxia adaptation of Aspergillus fumigatus

Project description:In the site of infection, the human fungal pathogen Aspergillus fumigatus faces dynamic changes in oxygen concentrations. The ability to survive in severely hypoxic environments during host invasion is one of important virulence traits of A. fumigatus. Therefore, investigation of hypoxia adaptation mechanisms of this pathogen may suggest potential targets for the development of antifungal therapies. Currently, an increasing number of reports has demonstrated that elevated production of intracellular reactive oxygen species (ROS) under low oxygen conditions plays a regulatory role in modulating cellular responses for adaptation to hypoxia. Our results confirmed raised amounts of intracellular ROS in A. fumigatus exposed to decreased oxygen levels. Moreover, nuclear accumulation of the oxidative stress response transcriptional factor AfYap1 was observed after two hours of low oxygen cultivation. For further analysis, we applied iodo-TMT labeling of redox-sensitive cysteine residues to identify proteins, which get reversibly oxidized and therefore regulated by hypoxic ROS after shifting oxygen content in the culture from 21% to 0.2%. For instance, proteins with important roles in maintaining redox balance and protein folding were modified after one hour of hypoxic cultivation. Redox proteomic investigation also revealed that a mitochondrial protein, designated as Coa6, was regulated by hypoxic ROS. A homologous protein in Saccharomyces cerevisiae was shown to be important for a respiratory chain complex IV assembly. Deletion of the gene encoding this protein in A. fumigatus resulted in complete absence of hypoxic growth, suggesting the significance of complex IV during adaptation of A. fumigatus to oxygen limiting conditions.

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Effect of amphotericin B on Aspergillus fumigatus

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Small RNA sequencing of Aspergillus fumigatus

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tRF & tiRNA sequencing of Aspergillus fumigatus

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