ArticleEukaryotic cell2012
Dsc orthologs are required for hypoxia adaptation, triazole drug responses, and fungal virulence in Aspergillus fumigatus.
Article in Eukaryotic cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 76 citations in OpenAlex.
- Functional Characterization of a Signal Peptide Peptidase inInternational journal of molecular sciences · 2026Article
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- Phosphatidic acid directly activates mTOR and then regulates SREBP to promote ganoderic acid biosynthesis under heat stress in Ganoderma lingzhi.Communications biology · 2024Article
- Article
- Aspergillus fumigatus Hypoxia Adaptation Is Critical for the Establishment of Fungal Keratitis.Investigative ophthalmology & visual science · 2024Article
- A bird's-eye view of the endoplasmic reticulum in filamentous fungi.Microbiology and molecular biology reviews : MMBR · 2024Review
- Development of the thermophilic fungus Myceliophthora thermophila into glucoamylase hyperproduction system via the metabolic engineering using improved AsCas12a variants.Microbial cell factories · 2023Article
- The Transcriptome Response to Azole Compounds inJournal of fungi (Basel, Switzerland) · 2023Article
- Dysfunction of Ras-GAP protein AfgapA contributes to hypoxia fitness in Aspergillus fumigatus.Current genetics · 2022Article
- Novel Insights intoJournal of fungi (Basel, Switzerland) · 2022Review
- The CCAAT-binding complex mediates azole susceptibility of Aspergillus fumigatus by suppressing SrbA expression and cleavage.MicrobiologyOpen · 2021Article
- The SREBP (Sterol Regulatory Element-Binding Protein) pathway: a regulatory bridge between carotenogenesis and sterol biosynthesis in the carotenogenic yeast Xanthophyllomyces dendrorhous.Biological research · 2021Review
- The dual role of SrbA from Paracoccidioides lutzii: a hypoxic regulator.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2021Article
- Development of a marker-free mutagenesis system using CRISPR-Cas9 in the pathogenic mould Aspergillus fumigatus.Fungal genetics and biology : FG & B · 2020Article
- Linking calcium signaling and mitochondrial function in fungal drug resistance.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- An Ssd1 Homolog Impacts Trehalose and Chitin Biosynthesis and Contributes to Virulence in Aspergillus fumigatus.mSphere · 2019Article
- Analysis of an Intrinsic Mycovirus Associated With Reduced Virulence of the Human Pathogenic FungusFrontiers in microbiology · 2019Article
- Oxygen-responsive transcriptional regulation of lipid homeostasis in fungi: Implications for anti-fungal drug development.Seminars in cell & developmental biology · 2018Review
- Aspergillus fumigatus morphology and dynamic host interactions.Nature reviews. Microbiology · 2017Review
- Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Hypoxia is an environmental stress encountered by Aspergillus fumigatus during invasive pulmonary aspergillosis (IPA). The ability of this mold to adapt to hypoxia is important for fungal virulence and genetically regulated in part by the sterol regulatory element binding protein (SREBP) SrbA. SrbA is required for fungal growth in the murine lung and to ultimately cause lethal disease in murine models of IPA. Here we identified and partially characterized four genes (dscA, dscB, dscC, and dscD, here referred to as dscA-D) with previously unknown functions in A. fumigatus that are orthologs of the Schizosaccharomyces pombe genes dsc1, dsc2, dsc3, and dsc4 (dsc1-4), which encode a Golgi E3 ligase complex critical for SREBP activation by proteolytic cleavage. A. fumigatus null dscA-D mutants displayed remarkable defects in hypoxic growth and increased susceptibility to triazole antifungal drugs. Consistent with the confirmed role of these genes in S. pombe, both ΔdscA and ΔdscC resulted in reduced cleavage of the SrbA precursor protein in A. fumigatus. Inoculation of corticosteroid immunosuppressed mice with ΔdscA and ΔdscC strains revealed that these genes are critical for A. fumigatus virulence. Reintroduction of SrbA amino acids 1 to 425, encompassing the N terminus DNA binding domain, into the ΔdscA strain was able to partially restore virulence, further supporting a mechanistic link between DscA and SrbA function. Thus, we have shown for the first time the importance of a previously uncharacterized group of genes in A. fumigatus that mediate hypoxia adaptation, fungal virulence, and triazole drug susceptibility and that are likely linked to regulation of SrbA function.
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