Project description:Aspergillus fumigatus is an important human pathogen and a leading fungal killer. This study aimed to determine the small RNA repertoire of A. fumigatus in conidia and mycelium grown for 24 or 48 hours in liquid culture.
Project description:Aspergillus fumigatus is an important human pathogen and a leading fungal killer. This study aimed to determine the tRNA fragment and tRNA half repertoire of A. fumigatus in wild-type conidia and mycelium grown for 24 or 48 hours in liquid culture.
Project description:Purpose: The goal of this study is to investigate the responses of HUVECs after the stimulation of conidia of A. fumigatus Methods: HUVECs were stimulated with conidia of Aspergillus fumigatus for 2 and 6 hours. Three biological repeats of stimulated cells or un-stimulated controls were send for RNA sequencing. Results: Using an optimized data analysis workflow, we mapped about 40 million sequence reads per sample to the human genome (build hg38) and identified round 80,000 transcripts in the HUVECs upon stimulation. Conclusions: Our resutls showed the detailed analysis of HUVECs transcriptomes upton conidia of Aspergillus fumigatus stimulation.
Project description:To investigate the influence of Aspergillus fumigatus on iron regulation in macrophages, we obtained macrophages in culture from human derived monocytes and co-cultured the monocyte-derived macrophages with Aspergillus conidia at a 1:1 ratio. We collected samples at 0, 2, 4, 6 and 8 hours and extracted RNA. We then performed gene expression profiling analysis using data obtained from RNA-seq of control macrophages and macrophage co-cultured with Aspergillus fumigatus at five time points.
Project description:The mechanism of action of the new antifungal compound 089 was identified in Saccharomyces cerevisiae. The compound had antifungal effects also on pathogenic fungi. While on Candida species the treatment induced cells death, on A. fumigatus strains it inhibited the conidia transition to hyphae. We carried out RNA sequencing analysis to evaluate at the molecular level the effect of the treatment on Aspergillus.
Project description:Microarray analysis was used to compare different divelopmental stages of the filamentous fungi Aspergillus fumigatus af293. Cells were grone for various times and comparisons made between: 1. Dormant conidia (0 hours) and isotropically expanding cells (1hr). 2. Dormant conidia (0 hours) and isotropically expanding cells (2hr) . 3. Dormant conidia (0 hours) and isotropically expanding cells (4hr). 4. Isotropically expanding cells (4hr) and polarity extending cells (6hr). 4. Isotropically expanding cells (4hr) and germ tube (8hr).
Project description:We report the gene expression level of Aspergillus fumigatus CEA17_ΔakuBKU80 strain in dormant conidia, in swollen conidia (after 4h of culture in Glucose 3%, Yeast Exrtract 1% liquid medium) and in germinated conidia (after 8h of culture in Glucose 3%, Yeast Extract 1% liquid medium after construction of an RNAseq library.
Project description:Plasmacytoid dendritic cells (pDCs) were initially considered as critical for innate immunity to viruses. However, our group has shown that pDCs bind to and inhibit the growth of Aspergillus fumigatus hyphae and that depletion of pDCs renders mice hypersusceptible to experimental aspergillosis. In this study, we examined pDC receptors responsible for hyphal recognition and downstream events in pDCs stimulated by A. fumigatus hyphae. Our data show that Dectin-2 but not Dectin-1 participates in hyphal recognition by pDCs and that Dectin-2 acts in cooperation with the FcRγ chain to trigger signaling responses. In addition, using confocal and electron microscopy we demonstrated that the interaction between pDCs and A. fumigatus induced the formation of pDC extracellular traps (pETs) containing DNA and citrullinated histone H3. Thus, these structures closely resembled those of neutrophil extracellular traps (NETs). Microarray analysis of the pDC transcriptome upon A. fumigatus infection demonstrated up-regulated expression of genes previously associated with viral infections or apoptosis. Moreover, the abundant expression of type I Interferon-encoding genes seen in CpG-stimulated pDCs was absent in the pDCs infected with A. fumigatus hyphae. Thus, human pDCs directly recognize A. fumigatus hyphae via Dectin-2. This interaction leads to formation of pET and triggers a distinct pattern of pDC gene expression.
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.