ArticleNature chemical biology2016
Dual action antifungal small molecule modulates multidrug efflux and TOR signaling.
Article in Nature chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 102 citations in OpenAlex.
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- Fpr1p mediates the synergistic effect of rapamycin or tacrolimus with caspofungin inJAC-antimicrobial resistance · 2026Article
- Soil Reservoirs of Antifungal-Resistant Fungi: Implications for Plant Disease Management with a Focus onMicroorganisms · 2026Review
- Article
- Synthetic Lethal Therapy Based on Dimorphism for Systemic Infection of Drug-Resistant Candida albicans.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Osh2 mediatesAntimicrobial agents and chemotherapy · 2025Article
- Antifungal Drugs for the Treatment of Invasive Fungal Infections-A Limited Therapeutic Toolbox Facing Growing Resistances.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Structure-guided optimization of small molecules targeting Yck2 as a strategy to combat Candida albicans.Nature communications · 2025Article
- Structure-guided optimization of small molecules targeting the yeast casein kinase, Yck2, as a therapeutic strategy to combat Candida albicans.Research square · 2025Article
- Use of gain-of-function suppressor screening to elucidateFrontiers in microbiology · 2025Article
- Lansoprazole interferes with fungal respiration and acts synergistically with amphotericin B against multidrug-resistantEmerging microbes & infections · 2024Article
- A dual-targeting antifungal is effective against multidrug-resistant human fungal pathogens.Nature microbiology · 2024Article
- Review
- Advancements and challenges in antifungal therapeutic development.Clinical microbiology reviews · 2024Review
- Casein kinase 2 complex: a central regulator of multiple pathobiological signaling pathways inmBio · 2024Article
- Proteasome inhibition as a therapeutic target for the fungal pathogenMicrobiology spectrum · 2023Article
- Azole potentiation in Candida species.PLoS pathogens · 2023Article
- Functional genomic analysis ofiScience · 2023Article
- Molecular mechanisms governing antifungal drug resistance.npj antimicrobials and resistance · 2023Review
- Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 10 institutions in 6 countries.
Funding
Abstract
There is an urgent need for new strategies to treat invasive fungal infections, which are a leading cause of human mortality. Here, we establish two activities of the natural product beauvericin, which potentiates the activity of the most widely deployed class of antifungal against the leading human fungal pathogens, blocks the emergence of drug resistance, and renders antifungal-resistant pathogens responsive to treatment in mammalian infection models. Harnessing genome sequencing of beauvericin-resistant mutants, affinity purification of a biotinylated beauvericin analog, and biochemical and genetic assays reveals that beauvericin blocks multidrug efflux and inhibits the global regulator TORC1 kinase, thereby activating the protein kinase CK2 and inhibiting the molecular chaperone Hsp90. Substitutions in the multidrug transporter Pdr5 that enable beauvericin efflux impair antifungal efflux, thereby impeding resistance to the drug combination. Thus, dual targeting of multidrug efflux and TOR signaling provides a powerful, broadly effective therapeutic strategy for treating fungal infectious disease that evades resistance.
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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.