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Effects of methylprednisolone on Aspergillus fumigatus 293 gene expression

ABSTRACT: Corticosteroid use has epidemiologically been associated with invasive aspergillosis. We found that hydrocortisone and MP in physiological concentrations cause a change in morphology of A. fumigatus 293 growth with a less dense core, and straighter outgrowth of longer hyphae. Treated with MP, we found a differential expression of genes annotated to cell wall structure, and to cell cycle programme compared to untreated control, which could explain the changes in morphology. The up-regulation of genes encoding for toxins, iron acquisition, and cell wall components enforcing oxidative stress resistance would theoretically result in a more pathogenic A. fumigatus phenotype. Upregulation of pathways involved in DNA-repair might indicate on genotoxic effects of MP.

ORGANISM(S): Aspergillus fumigatus Af293

PROVIDER: GSE46559 | GEO | 2014/05/01

SECONDARY ACCESSION(S): PRJNA200963

REPOSITORIES: GEO

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Effects of methylprednisolone on Aspergillus fumigatus 293 gene expression

Project description:Corticosteroid use has epidemiologically been associated with invasive aspergillosis. We found that hydrocortisone and MP in physiological concentrations cause a change in morphology of A. fumigatus 293 growth with a less dense core, and straighter outgrowth of longer hyphae. Treated with MP, we found a differential expression of genes annotated to cell wall structure, and to cell cycle programme compared to untreated control, which could explain the changes in morphology. The up-regulation of genes encoding for toxins, iron acquisition, and cell wall components enforcing oxidative stress resistance would theoretically result in a more pathogenic A. fumigatus phenotype. Upregulation of pathways involved in DNA-repair might indicate on genotoxic effects of MP. Examination of test setting with 0.5 microM methylprednisolone versus control setting without methylprednisolone. Identification of differentially expressed genes (DEGs) was performed on the pooled data of the 3 samples treated with MP versus the 3 untreated control samples, with correction for the total number of reads per group.

2014-05-01 | E-GEOD-46559 | biostudies-arrayexpress

Transcriptional profiling of ATCC46645 strain and isogenic ΔpacC Aspergillus fumigatus mutant during murine infection

Project description:In lung diseases caused by the major mould pathogen Aspergillus fumigatus the pulmonary epithelium is destroyed by invasive growth of fungal hyphae, a process thought to require fungal proteases. Here we show that the A. fumigatus pH-responsive transcription factor PacC governs expression of secreted proteases during invasive lung infections and is required for epithelial invasion and pathogenicity. In addition, A. fumigatus ΔpacC mutants aberrantly remodel the fungal cell wall during infection. This study defines distinct PacC-mediated mechanisms of host damage during pulmonary aspergillosis. ch1: treatment protocol

2014-10-20 | GSE54810 | GEO

Transcriptional profiling of ATCC46645 strain and isogenic M-NM-^TpacC Aspergillus fumigatus mutant during murine infection

Project description:In lung diseases caused by the major mould pathogen Aspergillus fumigatus the pulmonary epithelium is destroyed by invasive growth of fungal hyphae, a process thought to require fungal proteases. Here we show that the A. fumigatus pH-responsive transcription factor PacC governs expression of secreted proteases during invasive lung infections and is required for epithelial invasion and pathogenicity. In addition, A. fumigatus M-NM-^TpacC mutants aberrantly remodel the fungal cell wall during infection. This study defines distinct PacC-mediated mechanisms of host damage during pulmonary aspergillosis. ch1: treatment protocol Temporal transcriptional profiling of ATCC46645 strain and isogenic M-NM-^TpacC Aspergillus fumigatus mutant during murine infection

2014-10-20 | E-GEOD-54810 | biostudies-arrayexpress

Effect of amphotericin B on Aspergillus fumigatus

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. 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 microarray and proteomic methods. Keywords: Aspergillus fumigatus treated with amphotericin B for 24 hours Experiment was performed in dye swap manner from two different biological replicates

2010-05-26 | E-GEOD-10505 | biostudies-arrayexpress

Effect of amphotericin B on Aspergillus fumigatus

2008-02-14 | GSE10505 | GEO

Effect of Artemisinin on Aspergillus fumigatus gene expression program

Project description:We examined the antifungal activity of artemisinin against Aspergillus fumigatus (A. fumigatus), a pathogenic filamentous fungus responsible for allergic and invasive aspergillosis in humans and analyzed transcript profiles of the fungus on exposure to Artemisinin. A. fumigatus spores were cultured for 48 h and then treated with artemisinin (at MIC50 concentration) or solvent control (DMSO) for 3 h to study its transcriptomic profiles.

2011-05-11 | GSE21297 | GEO

Aspergillus fumigatus in blood reveals a "just wait and see" resting stage behavior

Project description:Objective: We analyzed changes in A. fumigatus gene expression profile at various stages of an in vitro model of aspergillosis to study the adaptation of A. fumigatus to the blood environment. Results: Most of virulence factors described to be involved in aspergillosis were not activated during the blood phase. We found three active processes to be activated in the later phase that may help to the adaptation: Iron homeostasis, a partial secondary metabolite cluster and the formation of detoxification enzymes. Conclusions: We propose that A. fumigatus is unable to grow in blood and it requires a metabolic change that allows the organism to shut down all uptake and energy-consume mechanisms, resulting in a resting mycelial stage.

2015-11-24 | GSE70227 | GEO

Functional genomics of Aspergillus fumigatus conidiospores interacting with human bronchial epithelial cells

Project description:The cells of the airway epithelium play critical roles in host defense to inhaled irritants, and in asthma pathogenesis. These cells are constantly exposed to conidiospores of the ubiquitous mould Aspergillus fumigatus, which are small enough to reach the alveoli. This exposure is asymptomatic in most individuals but can be associated with a spectrum of diseases ranging from asthma and allergic bronchopulmonary aspergillosis to aspergilloma and invasive aspergillosis. Airway epithelial cells have been shown to internalize A. fumigatus conidiospores in vitro, but the implications of this process for pathogenesis remain unclear. We have developed a cell culture model for this interaction using the 16HBE cell line and a transgenic A. fumigatus strain expressing green fluorescent protein. The transcriptional profiles of A. fumigatus conidiospores incubated in the presence or absence of human cells were compared, revealing significant changes in fungal gene expression in response to conidial interaction with cells.

2011-06-01 | GSE16630 | GEO

Functional genomics of human bronchial epithelial cells interacting with conidiospores of Aspergillus fumigatus

Project description:The cells of the airway epithelium play critical roles in host defense to inhaled irritants, and in asthma pathogenesis. These cells are constantly exposed to conidiospores of the ubiquitous mould Aspergillus fumigatus, which are small enough to reach the alveoli. This exposure is asymptomatic in most individuals but can be associated with a spectrum of diseases ranging from asthma and allergic bronchopulmonary aspergillosis to aspergilloma and invasive aspergillosis. Airway epithelial cells have been shown to internalize A. fumigatus conidiospores in vitro, but the implications of this process for pathogenesis remain unclear. We have developed a cell culture model for this interaction using the 16HBE cell line and a transgenic A. fumigatus strain expressing green fluorescent protein. Comparing the transcriptional profiles of control cells and cells exposed to A. fumigatus conidiospores using Agilent Whole Human Genome microarrays revealed significant changes in gene expression in response to the presence of conidiospores. The identification of biologically relevant responses validates this methodology, and motivates further work to characterize the interactions between A. fumigatus conidiospores and primary airway epithelial cells of normal and asthmatic origins.

2011-06-01 | GSE16628 | GEO

Long-term adaptation to hypoxic conditions - Febit transcriptome analysis

Project description:Aspergillus fumigatus is an opportunistic, airborne pathogen causing invasive aspergillosis in immunocompromised patients. During the infection process A. fumigatus is challenged by hypoxic microenvironments occurring in inflammatory, necrotic tissue. To gain further insights into the adaptation mechanism, A. fumigatus was cultivated in an oxygen-controlled chemostat under hypoxic and normoxic conditions. Transcriptome analysis revealed significant increases in transcripts associated with cell wall polysaccharide metabolism, amino acid and metal ion transport, nitrogen metabolism and glycolysis. A concomitant reduction in transcript levels was observed with cellular trafficking and G-protein coupled signaling. To learn more about the functional roles of hypoxia-induced transcripts we deleted A. fumigatus genes putatively involved in reactive nitrogen species detoxification (fhpA), NAD+ regeneration (frdA, osmA) nitrogen metabolism (niaD, niiA) and respiration (rcfB). We show that the NO-detoxifying flavohemoprotein fhpA is strongly induced by hypoxia independent of the nitrogen source, but is dispensable for hypoxic survival. By deleting the nitrate reductase gene niaD, the nitrite reductase gene niiA and the two fumarate reductases genes frdA and osmA, we found that alternative electron acceptors such as nitrate and fumarate do not have a significant impact on growth of A. fumigatus during hypoxia, but that functional mitochondrial respiratory chain complexes are essential under these conditions. Inhibition studies indicated that primarily complex III and IV play a crucial role in the hypoxic growth of A. fumigatus.

2014-07-01 | E-MTAB-2699 | biostudies-arrayexpress

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