Cited by 89Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Plant Pathogen Control

In Vitro Activity of Calcineurin and Heat Shock Protein 90 Inhibitors against Aspergillus fumigatus Azole- and Echinocandin-Resistant Strains

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Lamoth, Frédéric, Juvvadi, Praveen R., Gehrke, Christopher, Steinbach, William J.·2013·Antimicrobial Agents and Chemotherapy

Abstract

Due to the limited number of antifungals and the emergence of resistance, new therapies against invasive aspergillosis are needed. We show that calcineurin inhibitors are active in vitro against both azole- and echinocandin-resistant Aspergillus fumigatus strains. The heat shock protein 90 (Hsp90) inhibitor geldanamycin had modest activity when used alone, but its combination with caspofungin or tacrolimus (FK506) resulted in fungicidal activity against azole-resistant strains. Targeting the Hsp90-calcineurin axis is a promising alternative strategy against azole-resistant A. fumigatus strains.

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Authors
Lamoth, F., Juvvadi, P. R., Gehrke, C., & Steinbach, W. J.
Affiliations
  • Duke Medical Center (US)
  • Duke University (US)
Venue
Antimicrobial Agents and Chemotherapy
Published
2013-02
Volume
57
Issue
2
Pages
1035-1039
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
OpenAlex
W2120004156
Cited by
88
References
27
Citations by year
2026: 2 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 4 · 2021: 6 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 8 · 2016: 9 · 2015: 8 · 2014: 12 · 2013: 6
FWCI
5.74
Type
journal article
Language
en
Open access
Locations
  • Antimicrobial Agents and Chemotherapy (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (142746)
  • Ministerio de Economía y Competitividad
  • National Institute of Allergy and Infectious Diseases (R56AI077648)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Keywords
Aspergillus fumigatus, calcineurin inhibitors, Hsp90 inhibitors, geldanamycin, tacrolimus, caspofungin, azole resistance, echinocandin resistance, invasive aspergillosis, antifungal resistance, combination therapy, fungicidal activity
MeSH terms
Caspofungin, Antifungal Agents, Aspergillosis, Aspergillus fumigatus, Azoles, Drug Therapy, Combination, Microbial Sensitivity Tests, Benzoquinones, Tacrolimus, HSP90 Heat-Shock Proteins, Drug Resistance, Multiple, Fungal, Lactams, Macrocyclic, Echinocandins, Lipopeptides, Calcineurin Inhibitors

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