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ABSTRACT: Sirtuin E deacetylase is required for Aspergillus fumigatus full virulence

PROVIDER: PRJNA1029295 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28781290_1.fastq.gz	Fastqsanger.gz
	SRR28781290_2.fastq.gz	Fastqsanger.gz
	SRR28781291_1.fastq.gz	Fastqsanger.gz
	SRR28781291_2.fastq.gz	Fastqsanger.gz
	SRR28781292_1.fastq.gz	Fastqsanger.gz

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The Role of NAD+-dependent lysine deacetylases (Sirtuin) and their Inhibitors in Aspergillus fumigatus acetylome and virulence

Project description:Protein acetylation is a posttranslational modification that orchestrates gene regulation and various biological processes, such as fungal pathogenesis. One promising strategy for treating fungal infections is targeting the enzymes that regulate protein acetylation. Sirtuins, an NAD+-dependent lysine deacetylase, have been described as histone deacetylase and as regulators of secondary metabolism in various Aspergillus spp. However, the roles of sirtuin remain unclear. We employed a comprehensive set of experimental techniques, including gene deletion, phenotyping, in vivo virulence assays, metabolome analysis, transcriptome analysis, and acetylome analysis. Our findings reveal that sirtuins in A. fumigatus are intricately involved in crucial cellular processes such as cell wall integrity, secondary metabolite (SM) production, protease secretion, thermotolerance, and virulence. Notably, among the six sirtuins studied, AFSirE exerts a major influence on the phenotype of A. fumigatus. Furthermore, through acetylome analysis, we identified 42 and 260 proteins exhibiting differential acetylation in the AfSirE and SIRTko strains, respectively. Transcriptome data obtained from RNA sequencing (RNA-seq) demonstrated that sirtuins play a regulatory role in the expression of genes associated with SM production, cell wall component biosynthesis, and a variety of virulence factors.

2024-06-20 | PXD044964 | Pride

Expression data from Aspergillus nidulans FGSCA26 and SirAdelta grown for 24,48, and 72h

Project description:The sirA gene encodes a member of sirtuin protein that is NAD(+)-dependent histone deacetylase (HDAC) and ubiquitous in eukaryote. DNA microarray analyses for Aspergillus nidulans FGSCA26 (WT) strain and Gene disruptant of sirA (SirAd) indicated that genes for synthesizing secondary metabolic products such as sterigmatocystin, penicillin G, emericellamide, aspernidine A, xanthone, austinol, and siderophores are down-regulated by SirA. Aspergillus nidulans WT and SirAd strains were cultured in 200 ml of GMM at 30Â°C for 24, 48, and 72 h, and their total RNA was purified as described above.

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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

Ewald2021 - Innate immune response during invasive aspergillosis by dynamic optimization

Project description:Aspergillus fumigatus is an important human fungal pathogen and its conidia are constantly inhaled by humans. In immunocompromised individuals, conidia can grow out as hyphae that damage lung epithelium. The resulting invasive aspergillosis is associated with devastating mortality rates. Since infection is a race between the innate immune system and the outgrowth of A. fumigatus conidia, we use dynamic optimization to obtain insight into the recruitment and depletion of alveolar macrophages and neutrophils. We illustrate by modeling the active, but so far neglected, major role of alveolar epithelial cells in phagocytosis and cytokine release as well as the importance of fungal growth states for virulence. Hence, we discovered that germination speed is a key virulence trait of fungal pathogens due to the vulnerability of conidia against host defense. We proved this by linking measured germination kinetics of four Aspergillus spp. with their cytotoxicity against epithelial cells in silico and in vitro.Furthermore, we could reveal by modeling and ex vivo measurements, that epithelial cells are not only important phagocytes to clear conidia, but also potent mediators of cytokine release. In conclusion, our findings illustrate an underestimated role of epithelial cells in invasive aspergillosis. Further, our model affirms the importance of neutrophils and underlines that the role of macrophages in invasive aspergillosis remains elusive. We expect that our model will contribute to improvement of treatment protocols by focusing on the critical components of immune response to fungi but also fungal virulence.

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Transcription profiling of Aspergillus fumigatus isolates following laboratory culture or initiation of infection in the neutropenic murine lung to understand how metabolic and nutritional factors governing adaptation to the host niche contribute to virulence

Project description:To understand how metabolic and nutritional factors governing adaptation to the host niche contribute to the virulence of Aspergillus fumigatus we compared transcriptomes of developmentally matched A.fumigatus isolates following laboratory culture or initiation of infection in the neutropenic murine lung.

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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.

2005-05-15 | E-MEXP-333 | biostudies-arrayexpress

Identification of the early exoproteome of pathogenic Aspergilli, Aspergillus flavus and Aspergillus fumigatus

Project description:We identified the proteins secreted by A. flavus and A. fumigatus conidia during the early stages of growth. A comparative analysis was done between the exoproteome of the two species to identify the core proteins that were common between the two Aspergilli as well as species specific signature protiens. The common proteins included cell wall polysaccharide modifying enzymes and those required for nutrient acquisition. The core proteome is an indication that A. flavus and A. fumigatus share the common events during germination and growth. On the other hand, each Aspergillus had a unique subset of proteins that could be potential virulence factors or effector molecules. This species-specific exoprotein signature probably reflects the specific requirements of the Aspergillus pathogen to establish an infection in a particular niche.

2025-01-17 | PXD012982 | Pride

sRNA-seq of Aspergillus fumigatus RNAi double knockouts

Project description:The RNA interference (RNAi) pathway has evolved numerous functionalities in eukaryotes, with many on display in Kingdom Fungi. RNAi can regulate gene expression, facilitate drug resistance, or even be altogether lost to improve virulence potential in some fungal pathogens. In the WHO fungal priority pathogen, Aspergillus fumigatus, the RNAi system is known to be intact and functional. To extend our limited understanding of A. fumigatus RNAi, we performed a multi-condition sRNA-seq analysis comparing expression of several RNAi double knockout mutants with the wild-type strain in conidia and mycelium grown for 24 or 48 hours.

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Expression data from Aspergillus nidulans FGSCA26 and SirAdelta grown for 24,48, and 72h

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Project description:Aspergillus fumigatus HapX-mediated iron starvation adaption is required for virulence.

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