ArticleAntimicrobial agents and chemotherapy2015
Hsp70 and the Cochaperone StiA (Hop) Orchestrate Hsp90-Mediated Caspofungin Tolerance in Aspergillus fumigatus.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Heat Shock Proteins in Medically Relevant Fungal Pathogens: From Molecular Chaperones to Virulence Factors and Therapeutic Targets.Journal of fungi (Basel, Switzerland) · 2026Review
- Exploring a Therapeutic Gold Mine: The Antifungal Potential of the Gold-Based Antirheumatic Drug Auranofin.International journal of molecular sciences · 2025Review
- Cell walls of filamentous fungi - challenges and opportunities for biotechnology.Applied microbiology and biotechnology · 2025Review
- Fungal Extracellular Vesicle Proteins with Potential in Biological Interaction.Molecules (Basel, Switzerland) · 2024Review
- Chaperone Networks in Fungal Pathogens of Humans.Journal of fungi (Basel, Switzerland) · 2021Review
- Aspergillus fumigatus Hsp90 interacts with the main components of the cell wall integrity pathway and cooperates in heat shock and cell wall stress adaptation.Cellular microbiology · 2021Article
- The Heat Shock Transcription Factor HsfA Is Essential for Thermotolerance and Regulates Cell Wall Integrity inFrontiers in microbiology · 2021Article
- Biotinylated Surfome Profiling Identifies Potential Biomarkers for Diagnosis and Therapy of Aspergillus fumigatus Infection.mSphere · 2020Article
- Phosphoproteomics of Aspergillus fumigatus Exposed to the Antifungal Drug Caspofungin.mSphere · 2020Article
- Study of Humoral Responses againstVaccines · 2019Article
- Echinocandins for the Treatment of Invasive Aspergillosis: from Laboratory to Bedside.Antimicrobial agents and chemotherapy · 2019Review
- Article
- Adapting to stress - chaperome networks in cancer.Nature reviews. Cancer · 2018Review
- Proteomics as a Tool to Identify New Targets Against Aspergillus and Scedosporium in the Context of Cystic Fibrosis.Mycopathologia · 2018Review
- An insight into new strategies to combat antifungal drug resistance.Drug design, development and therapy · 2018Review
- Molecular and cellular responses of the pathogenic fungus Lomentospora prolificans to the antifungal drug voriconazole.PloS one · 2017Article
- Heat shock protein 90 is required for sexual and asexual development, virulence, and heat shock response in Fusarium graminearum.Scientific reports · 2016Article
- The Hsp90 Co-chaperones Sti1, Aha1, and P23 Regulate Adaptive Responses to Antifungal Azoles.Frontiers in microbiology · 2016Article
- Systematic Identification of Anti-Fungal Drug Targets by a Metabolic Network Approach.Frontiers in molecular biosciences · 2016Article
- Calcineurin Orchestrates Hyphal Growth, Septation, Drug Resistance and Pathogenesis of Aspergillus fumigatus: Where Do We Go from Here?Pathogens (Basel, Switzerland) · 2015Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aspergillus fumigatus is the primary etiologic agent of invasive aspergillosis (IA), a major cause of death among immunosuppressed patients. Echinocandins (e.g., caspofungin) are increasingly used as second-line therapy for IA, but their activity is only fungistatic. Heat shock protein 90 (Hsp90) was previously shown to trigger tolerance to caspofungin and the paradoxical effect (i.e., decreased efficacy of caspofungin at higher concentrations). Here, we demonstrate the key role of another molecular chaperone, Hsp70, in governing the stress response to caspofungin via Hsp90 and their cochaperone Hop/Sti1 (StiA in A. fumigatus). Mutation of the StiA-interacting domain of Hsp70 (C-terminal EELD motif) impaired thermal adaptation and caspofungin tolerance with loss of the caspofungin paradoxical effect. Impaired Hsp90 function and increased susceptibility to caspofungin were also observed following pharmacologic inhibition of the C-terminal domain of Hsp70 by pifithrin-μ or after stiA deletion, further supporting the links among Hsp70, StiA, and Hsp90 in governing caspofungin tolerance. StiA was not required for the physical interaction between Hsp70 and Hsp90 but had distinct roles in the regulation of their function in caspofungin and heat stress responses. In conclusion, this study deciphering the physical and functional interactions of the Hsp70-StiA-Hsp90 complex provided new insights into the mechanisms of tolerance to caspofungin in A. fumigatus and revealed a key C-terminal motif of Hsp70, which can be targeted by specific inhibitors, such as pifithrin-μ, to enhance the antifungal activity of caspofungin against A. fumigatus.
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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.