Aspergillus fumigatus
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ABSTRACT:
PROVIDER: PRJNA122297 | ENA |
REPOSITORIES: ENA
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Project description:The opportunistic pathogenic mold Aspergillus fumigatus is an increasing cause of morbidity and mortality in immunocompromised and, in part, immunocompetent patients. Like bacteria or yeast, A. fumigatus can grow in multicellular communities by the formation of a hyphal network encased in an extracellular matrix. Here, we describe the proteome and transcriptome of planktonic and biofilm-grown A. fumigatus mycelium after 24h and 48h. A biofilm- and time-dependent regulation of many proteins and genes of the primary metabolism indicates a developmental stage of the young biofilm at 24h, which demands energy. At a matured biofilm phase, metabolic activity seems to be reduced. However, genes encoding hydrophobins and proteins involved in the biosynthesis of secondary metabolites were significantly upregulated. In particular, proteins of the gliotoxin secondary metabolite gene cluster were induced in biofilm cultures. This was confirmed by RT-PCR and by detection of this immunologically active mycotoxin in culture supernatants using HPLC analysis. The enhanced production of gliotoxin by in vitro formed biofilms reported here may play also a significant role under in vivo conditions. It may confer A. fumigatus protection from the host immune system and also enable its survival and persistence in chronic lung infections such as aspergilloma. Comparison of biofilm and submers cultures at 24h and 48h after induction.
2010-07-01 | E-GEOD-19430 | biostudies-arrayexpress
Project description:The opportunistic pathogenic mold Aspergillus fumigatus is an increasing cause of morbidity and mortality in immunocompromised and, in part, immunocompetent patients. Like bacteria or yeast, A. fumigatus can grow in multicellular communities by the formation of a hyphal network encased in an extracellular matrix. Here, we describe the proteome and transcriptome of planktonic and biofilm-grown A. fumigatus mycelium after 24h and 48h. A biofilm- and time-dependent regulation of many proteins and genes of the primary metabolism indicates a developmental stage of the young biofilm at 24h, which demands energy. At a matured biofilm phase, metabolic activity seems to be reduced. However, genes encoding hydrophobins and proteins involved in the biosynthesis of secondary metabolites were significantly upregulated. In particular, proteins of the gliotoxin secondary metabolite gene cluster were induced in biofilm cultures. This was confirmed by RT-PCR and by detection of this immunologically active mycotoxin in culture supernatants using HPLC analysis. The enhanced production of gliotoxin by in vitro formed biofilms reported here may play also a significant role under in vivo conditions. It may confer A. fumigatus protection from the host immune system and also enable its survival and persistence in chronic lung infections such as aspergilloma.
2010-07-01 | GSE19430 | GEO
Project description:In patients with chronic pulmonary disease colonization with the mold Aspergillus fumigatus is associated with declining pulmonary function and obstructive airway disease. One potential effector of this inflammatory response is the pulmonary mast cell. In vitro studies have demonstrated that A. fumigatus contact induces IgE-independent mast cell degranulation. Conversely, the Aspergillus secondary metabolite gliotoxin has been shown to suppress mast cell activation. These contradictory results emphasize the need for a better understanding of the interactions between A. fumigatus and mast cells. Thus, the objective of this work was to identify A. fumigatus genes that are differentially regulated upon exposure to mast cells. Transcriptional profiling experiments indicated that, in addition to genes encoding for iron acquisition systems, allergens and putative virulence factors, genes from the gliotoxin biosynthesis cluster were significantly down-regulated upon exposure to mast cells. Globally, the results from this study provide insight into the A. fumigatus response to mast cells and suggest that one mechanism by which the host may circumvent the effects of gliotoxin is via the suppression of fungal gliotoxin synthesis by mast cells.
2012-03-02 | GSE27610 | GEO
Project description:The fungal pathogen Aspergillus fumigatus is frequently cultured from the sputum of cystic fibrosis (CF) patients along with the bacterium, Pseudomonas aeruginosa. A. fumigatus secretes a range of secondary metabolites, and one of these, gliotoxin, has inhibitory effects on the host immune response. In this study, the effect of P. aeruginosa culture filtrate (CuF) on fungal growth and gliotoxin production was investigated. Exposure of A. fumigatus hyphae to P. aeruginosa cells induced increased production of gliotoxin and a decrease in fungal growth. In contrast exposure of A. fumigatus hyphae to P. aeruginosa CuF lead to increased growth and decreased gliotoxin production. Quantitative proteomic analysis was employed to characterize the proteomic response of A. fumigatus upon exposure to P. aeruginosa CuF. Changes in the profile of proteins involved with secondary metabolite biosynthesis (gliotoxin, fumagillin, pseurotin A), and changes to the abundance of proteins involved in oxidative stress (e.g. formate dehydrogenase) and detoxification (e.g. thioredoxin reductase) were observed, suggesting that the bacterial secretome has a profound effect on the fungal proteome. Alterations in the abundance of proteins involved in detoxification and oxidative stress, highlight the ability of A. fumigatus to differentially regulate protein synthesis in response to environmental stresses imposed by competitors such as P. aeruginosa. Such responses may ultimately have serious detrimental effects on the host.
2023-03-10 | PXD030171 | Pride
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.
2005-05-15 | E-MEXP-333 | biostudies-arrayexpress
Project description:<p>Gliotoxin is a secondary metabolite produced by Aspergillus fumigatus, known to play a significant role in immune regulation and virulence phenotypes. This study investigates how the deletion of gliotoxin biosynthesis remodels the metabolic state of A. fumigatus and subsequently affects host immune responses. We employed a multi-omics approach, integrating fungal metabolomics and host transcriptomics data, to assess the impact of gliotoxin deletion on intra- and extracellular metabolic processes. The results showed that the loss of gliotoxin biosynthesis significantly altered the metabolic profile of A. fumigatus, with distinct changes observed in metabolites from both fungal mycelia and culture supernatants. These metabolic alterations were closely linked to changes in host cellular immune-related pathways. Notably, in macrophages and epithelial cells, treatment with gliotoxin led to significant changes in immune gene expression, revealing its role in modulating host immune responses.</p><p>Furthermore, treating macrophages with gliotoxin inhibited the secretion of inflammatory cytokines and reduced the cells' phagocytic capacity for A. fumigatus conidia, indicating that gliotoxin may play a role in suppressing host defense mechanisms. However, transcriptomic analysis also suggested that exposure to gliotoxin could promote the expression of certain immune genes, pointing to a complex interaction between the fungal metabolite and the host immune system. Through integrative analysis, we identified key metabolic and immune pathways affected by gliotoxin. These findings provide new insights into the impact of gliotoxin deletion on fungal virulence and host immunity, and offer a theoretical basis for potential therapeutic strategies in managing Aspergillus fumigatus infections.</p>
2026-05-11 | MTBLS14012 | MetaboLights
Project description:<p>Gliotoxin is a secondary metabolite produced by Aspergillus fumigatus, known to play a significant role in immune regulation and virulence phenotypes. This study investigates how the deletion of gliotoxin biosynthesis remodels the metabolic state of A. fumigatus and subsequently affects host immune responses. We employed a multi-omics approach, integrating fungal metabolomics and host transcriptomics data, to assess the impact of gliotoxin deletion on intra- and extracellular metabolic processes. The results showed that the loss of gliotoxin biosynthesis significantly altered the metabolic profile of A. fumigatus, with distinct changes observed in metabolites from both fungal mycelia and culture supernatants. These metabolic alterations were closely linked to changes in host cellular immune-related pathways. Notably, in macrophages and epithelial cells, treatment with gliotoxin led to significant changes in immune gene expression, revealing its role in modulating host immune responses.</p><p>Furthermore, treating macrophages with gliotoxin inhibited the secretion of inflammatory cytokines and reduced the cells' phagocytic capacity for A. fumigatus conidia, indicating that gliotoxin may play a role in suppressing host defense mechanisms. However, transcriptomic analysis also suggested that exposure to gliotoxin could promote the expression of certain immune genes, pointing to a complex interaction between the fungal metabolite and the host immune system. Through integrative analysis, we identified key metabolic and immune pathways affected by gliotoxin. These findings provide new insights into the impact of gliotoxin deletion on fungal virulence and host immunity, and offer a theoretical basis for potential therapeutic strategies in managing Aspergillus fumigatus infections.</p>
2026-05-11 | MTBLS14011 | MetaboLights
Project description:Glucose is a widely used carbon source in laboratory practice to culture Aspergillus fumigatus, however, glucose availability is often low in its “natural habitats” including the human body. We used a physiological–transcriptomical approach to reveal differences between A. fumigatus Af293 cultures incubated on glucose, glucose and peptone, peptone (carbon limitation), or without any carbon source (carbon starvation). Autolytic cell wall degradation was upregulated by both carbon starvation and limitation. The importance of autolytic cell wall degradation in adaptation to carbon stress was also highlighted by approximately 12.4% of the A. fumigatus genomes harbor duplication of genes involved in N-acetyl glucosamine utilization. Glucose withdrawal increased redox imbalance, altered both the transcription of antioxidative enzyme genes and oxidative stress tolerance, downregulated iron acquisition, but upregulated heme protein genes. Transcriptional activity of the Gliotoxin cluster was low in all experiments, while the Fumagillin cluster showed substantial activity both on glucose and under carbon starvation, and the Hexadehydro-astechrome cluster only on glucose. We concluded that glucose withdrawal substantially modified the physiology of A. fumigatus including processes that contribute to virulence. This may explain the challenge of predicting the in vivo behavior of A. fumigatus based on data from glucose rich cultures.
2022-12-09 | GSE216000 | GEO
Project description:The fungal pathogen Aspergillus fumigatus is frequently cultured from the sputum of cystic fibrosis (CF) patients along with the bacterium, Pseudomonas aeruginosa. A. fumigatus secretes a range of secondary metabolites, and one of these, gliotoxin, has inhibitory effects on the host immune response. In this study, the effect of P. aeruginosa culture filtrate (CuF) on fungal growth and gliotoxin production was investigated. Exposure of A. fumigatus hyphae to P. aeruginosa cells induced increased production of gliotoxin and a decrease in fungal growth. In contrast exposure of A. fumigatus hyphae to P. aeruginosa CuF lead to increased growth and decreased gliotoxin production. Quantitative proteomic analysis was employed to characterize the proteomic response of A. fumigatus upon exposure to P. aeruginosa CuF. Changes in the profile of proteins involved with secondary metabolite biosynthesis (gliotoxin, fumagillin, pseurotin A), and changes to the abundance of proteins involved in oxidative stress (e.g. formate dehydrogenase) and detoxification (e.g. thioredoxin reductase) were observed, suggesting that the bacterial secretome has a profound effect on the fungal proteome. Alterations in the abundance of proteins involved in detoxification and oxidative stress, highlight the ability of A. fumigatus to differentially regulate protein synthesis in response to environmental stresses imposed by competitors such as P. aeruginosa. Such responses may ultimately have serious detrimental effects on the host.
2023-03-11 | PXD031565 | Pride
Project description:Amphotericin B (AMB) is the most widely used polyene antifungal drug for the treatment of systemic fungal infections including invasive aspergillosis. We aimed to understand molecular targets of AMB in Aspergillus fumigatus (Afu) by genomic approaches. Keywords: Aspergillus fumigatus treated with amphotericin B for 24 hours
2008-02-14 | GSE10505 | GEO