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

ABSTRACT: 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.

ORGANISM(S): Aspergillus fumigatus

PROVIDER: GSE70227 | GEO | 2015/11/24

SECONDARY ACCESSION(S): PRJNA287921

REPOSITORIES: GEO

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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. We performed gene expression profile by sequencing mRNA of A. fumigatus that were growm under two conditions, Minimal Medium (M) and human blood (B), and at different times: before placing the fungus in the final medium (pre), at 30' and at 180', with 2 biological replicates per condition.

2015-11-24 | E-GEOD-70227 | biostudies-arrayexpress

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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.

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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. Using fluorescence-activated cell sorting (FACS), cells directly interacting with conidiospores and cells not associated with any conidiospores were sorted into separate samples. Transcriptional profiling of these samples using Agilent Whole Human Genome microarrays revealed significant changes in gene expression in response to interaction with 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.

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

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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. Gene expression levels were investigated in A. fumigatus conidiospores incubated in the presence or absence of 16HBE cells for 6 hours. Four independent samples were analysed for each of these conditions, using JCVI PFGRC Aspergillus fumigatus Version 3 microarrays, with a dye-swap experimental design.

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