ArticleEukaryotic cell2012
Heat shock protein 90 is required for conidiation and cell wall integrity 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 86 papers.
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Who cites it
86 citing papers in PubMed, 132 citations in OpenAlex.
- Article
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- A stress responsive protein contributes to pyomelanin biosynthesis and cell wall stress adaptation inFrontiers in microbiology · 2026Article
- Transcriptomic Analysis Reveals Molecular Mechanisms Underpinning Mycovirus-Mediated Hypervirulence inJournal of fungi (Basel, Switzerland) · 2025Article
- Histopathological observation andFrontiers in microbiology · 2025Article
- MaPom1, a Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase, Positively Regulates Thermal and UV-B Tolerance inInternational journal of molecular sciences · 2024Article
- Interdisciplinary approaches for the discovery of novel antifungals.Trends in molecular medicine · 2024Review
- Retracing the evolution ofMicrobiology and molecular biology reviews : MMBR · 2024Review
- Old and new strategies in therapy and diagnosis against fungal infections.Applied microbiology and biotechnology · 2024Review
- Promising immunotherapeutic targets for treating candidiasis.Frontiers in cellular and infection microbiology · 2024Review
- An Insight into the Repurposing of Phytoconstituents obtained from Delhi's Aravalli Biodiversity Park as Antifungal Agents.Infectious disorders drug targets · 2024Article
- Roles of Hsp90 in Candida albicans morphogenesis and virulence.Current opinion in microbiology · 2023Review
- Insights and Perspectives on the Role of Proteostasis and Heat Shock Proteins in Fungal Infections.Microorganisms · 2023Review
- A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi.Nature communications · 2023Article
- Soil-BorneInternational journal of molecular sciences · 2023Review
- Potential Antifungal Targets forInternational journal of molecular sciences · 2022Review
- Genomic Approaches to Antifungal Drug Target Identification and Validation.Annual review of microbiology · 2022Review
- Novel Treatment Approach for Aspergilloses by Targeting Germination.Journal of fungi (Basel, Switzerland) · 2022Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Heat shock protein 90 (Hsp90) is a eukaryotic molecular chaperone. Its involvement in the resistance of Candida albicans to azole and echinocandin antifungals is well established. However, little is known about Hsp90's function in the filamentous fungal pathogen Aspergillus fumigatus. We investigated the role of Hsp90 in A. fumigatus by genetic repression and examined its cellular localization under various stress conditions. Failure to generate a deletion strain of hsp90 suggested that it is essential. Genetic repression of Hsp90 was achieved by an inducible nitrogen-dependent promoter (pniiA-Hsp90) and led to decreased spore viability, decreased hyphal growth, and severe defects in germination and conidiation concomitant with the downregulation of the conidiation-specific transcription factors brlA, wetA, and abaA. Hsp90 repression potentiated the effect of cell wall inhibitors affecting the β-glucan structure of the cell wall (caspofungin, Congo red) and of the calcineurin inhibitor FK506, supporting a role in regulating cell wall integrity pathways. Moreover, compromising Hsp90 abolished the paradoxical effect of caspofungin. Pharmacological inhibition of Hsp90 by geldanamycin and its derivatives (17-AAG and 17-DMAG) resulted in similar effects. C-terminal green fluorescent protein (GFP) tagging of Hsp90 revealed mainly cytosolic distribution under standard growth conditions. However, treatment with caspofungin resulted in Hsp90 accumulation at the cell wall and at sites of septum formation, further highlighting its role in cell wall stress compensatory mechanisms. Targeting Hsp90 with fungal-specific inhibitors to cripple stress response compensatory pathways represents an attractive new antifungal strategy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.