ArticlePloS one2016
Sterol Regulatory Element Binding Protein (Srb1) Is Required for Hypoxic Adaptation and Virulence in the Dimorphic Fungus Histoplasma capsulatum.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- How Histoplasma Evades the Human Immune System.Acta medica academica · 2025Review
- Elevated carbon dioxide enhances the growth and reduces the antifungal susceptibility ofMicrobiology spectrum · 2025Article
- Recent Advances in Understanding the Human Fungal Pathogen Hypoxia Response in Disease Progression.Annual review of microbiology · 2023Review
- Article
- The dual role of SrbA from Paracoccidioides lutzii: a hypoxic regulator.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2021Article
- Differential miRNA Expression in Human Macrophage-Like Cells Infected withJournal of fungi (Basel, Switzerland) · 2021Article
- Detection of Low Oxygen Microenvironments in a Murine Model of Invasive Pulmonary Aspergillosis Using Pimonidazole.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Article
- Remodeling of theVaccines · 2020Article
- Hypoxia: A Double-Edged Sword During Fungal Pathogenesis?Frontiers in microbiology · 2020Review
- Differentiation of the fungus Histoplasma capsulatum into a pathogen of phagocytes.Current opinion in microbiology · 2017Review
- Functional analysis of two sterol regulatory element binding proteins in Penicillium digitatum.PloS one · 2017Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The Histoplasma capsulatum sterol regulatory element binding protein (SREBP), Srb1 is a member of the basic helix-loop-helix (bHLH), leucine zipper DNA binding protein family of transcription factors that possess a unique tyrosine (Y) residue instead of an arginine (R) residue in the bHLH region. We have determined that Srb1 message levels increase in a time dependent manner during growth under oxygen deprivation (hypoxia). To further understand the role of Srb1 during infection and hypoxia, we silenced the gene encoding Srb1 using RNA interference (RNAi); characterized the resulting phenotype, determined its response to hypoxia, and its ability to cause disease within an infected host. Silencing of Srb1 resulted in a strain of H. capsulatum that is incapable of surviving in vitro hypoxia. We found that without complete Srb1 expression, H. capsulatum is killed by murine macrophages and avirulent in mice given a lethal dose of yeasts. Additionally, silencing Srb1 inhibited the hypoxic upregulation of other known H. capsulatum hypoxia-responsive genes (HRG), and genes that encode ergosterol biosynthetic enzymes. Consistent with these regulatory functions, Srb1 silenced H. capsulatum cells were hypersensitive to the antifungal azole drug itraconazole. These data support the theory that the H. capsulatum SREBP is critical for hypoxic adaptation and is required for H. capsulatum virulence.
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