ArticleInfection and immunity2016
Identification and Characterization of a Novel Aspergillus fumigatus Rhomboid Family Putative Protease, RbdA, Involved in Hypoxia Sensing and Virulence.
Article in Infection and immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
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- Mining Genetically Encoded Biosensors from Filamentous Fungi.Journal of fungi (Basel, Switzerland) · 2026Review
- The cyclase-associated protein contributes to antifungal susceptibility and virulence inEmerging microbes & infections · 2025Article
- Chemical Blockage of the Mitochondrial Rhomboid Protease PARL by Novel Ketoamide Inhibitors Reveals Its Role in PINK1/Parkin-Dependent Mitophagy.Journal of medicinal chemistry · 2023Article
- Characterization and engineering of the xylose-inducibleMetabolic engineering communications · 2022Article
- Engineering the amoeba Dictyostelium discoideum for biosynthesis of a cannabinoid precursor and other polyketides.Nature biotechnology · 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
- Development of a CRISPR/Cpf1 system for targeted gene disruption in Aspergillus aculeatus TBRC 277.BMC biotechnology · 2021Article
- Aspergillus fumigatus tryptophan metabolic route differently affects host immunity.Cell reports · 2021Article
- Development of a marker-free mutagenesis system using CRISPR-Cas9 in the pathogenic mould Aspergillus fumigatus.Fungal genetics and biology : FG & B · 2020Article
- Aspergillus fumigatus and Aspergillosis in 2019.Clinical microbiology reviews · 2019Review
- Menacing Mold: Recent Advances in Aspergillus Pathogenesis and Host Defense.Journal of molecular biology · 2019Review
- Analysis of an Intrinsic Mycovirus Associated With Reduced Virulence of the Human Pathogenic FungusFrontiers in microbiology · 2019Article
- The Lysine Deacetylase RpdA Is Essential for Virulence inFrontiers in microbiology · 2019Article
- Embedded in the Membrane: How Lipids Confer Activity and Specificity to Intramembrane Proteases.The Journal of membrane biology · 2018Article
- Study of Azole - Resistant andOpen access Macedonian journal of medical sciences · 2018Article
- Microtubules are reversibly depolymerized in response to changing gaseous microenvironments withinMolecular biology of the cell · 2017Article
- Regulation of Sterol Biosynthesis in the Human Fungal PathogenFrontiers in microbiology · 2017Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aspergillus fumigatus is the most common pathogenic mold infecting humans and a significant cause of morbidity and mortality in immunocompromised patients. In invasive pulmonary aspergillosis, A. fumigatus spores are inhaled into the lungs, undergoing germination and invasive hyphal growth. The fungus occludes and disrupts the blood vessels, leading to hypoxia and eventual tissue necrosis. The ability of this mold to adapt to hypoxia is regulated in part by the sterol regulatory element binding protein (SREBP) SrbA and the DscA to DscD Golgi E3 ligase complex critical for SREBP activation by proteolytic cleavage. Loss of the genes encoding these proteins results in avirulence. To identify novel regulators of hypoxia sensing, we screened the Neurospora crassa gene deletion library under hypoxia and identified a novel rhomboid family protease essential for hypoxic growth. Deletion of the A. fumigatus rhomboid homolog rbdA resulted in an inability to grow under hypoxia, hypersensitivity to CoCl2, nikkomycin Z, fluconazole, and ferrozine, abnormal swollen tip morphology, and transcriptional dysregulation-accurately phenocopying deletion of srbA. In vivo, rbdA deletion resulted in increased sensitivity to phagocytic killing, a reduced inflammatory Th1 and Th17 response, and strongly attenuated virulence. Phenotypic rescue of the ΔrbdA mutant was achieved by expression and nuclear localization of the N terminus of SrbA, including its HLH domain, further indicating that RbdA and SrbA act in the same signaling pathway. In summary, we have identified RbdA, a novel putative rhomboid family protease in A. fumigatus that mediates hypoxia adaptation and fungal virulence and that is likely linked to SrbA cleavage and activation.
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