ArticleProceedings of the National Academy of Sciences of the United States of America2007
High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 251 citations in OpenAlex.
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- Advances in the use of entomopathogenic fungi to control ixodid ticks.Revista brasileira de parasitologia veterinaria = Brazilian journal of veterinary parasitology : Orgao Oficial do Colegio Brasileiro de Parasitologia Veterinaria · 2026Review
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- Beauvericin Reverses Epithelial-to-Mesenchymal Transition in Triple-Negative Breast Cancer Cells through Regulation of Notch Signaling and Autophagy.ACS pharmacology & translational science · 2024Article
- The atypical antipsychotic aripiprazole alters the outcome of disseminatedInfection and immunity · 2024Article
- ABC transporter inhibition by beauvericin partially overcomes drug resistance inAntimicrobial agents and chemotherapy · 2024Article
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- The atypical antipsychotic aripiprazole alters the outcome of disseminatedbioRxiv : the preprint server for biology · 2024Article
- Harnessing machine learning to find synergistic combinations for FDA-approved cancer drugs.Scientific reports · 2024Article
- Models for Inducing Experimental Cryptococcosis in Mice.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Development of constitutively synergistic nanoformulations to enhance chemosensitivity in T-cell leukemia.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- On the Potential Role of the (Pseudo-) Jahn-Teller Effect in the Membrane Transport Processes: Enniatin B and Beauvericin.Molecules (Basel, Switzerland) · 2023Article
- Azole potentiation in Candida species.PLoS pathogens · 2023Article
- Developing synergistic drug combinations to restore antibiotic sensitivity in drug-resistantAntimicrobial agents and chemotherapy · 2023Article
- Novel Sulfonylurea Derivatives as Potential Antimicrobial Agents: Chemical Synthesis, Biological Evaluation, and Computational Study.Antibiotics (Basel, Switzerland) · 2023Article
- Microbial cell factories based on filamentous bacteria, yeasts, and fungi.Microbial cell factories · 2023Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
31 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The high mortality rate of immunocompromised patients with fungal infections and the limited availability of highly efficacious and safe agents demand the development of new antifungal therapeutics. To rapidly discover such agents, we developed a high-throughput synergy screening (HTSS) strategy for novel microbial natural products. Specifically, a microbial natural product library was screened for hits that synergize the effect of a low dosage of ketoconazole (KTC) that alone shows little detectable fungicidal activity. Through screening of approximately 20,000 microbial extracts, 12 hits were identified with broad-spectrum antifungal activity. Seven of them showed little cytotoxicity against human hepatoma cells. Fractionation of the active extracts revealed beauvericin (BEA) as the most potent component, because it dramatically synergized KTC activity against diverse fungal pathogens by a checkerboard assay. Significantly, in our immunocompromised mouse model, combinations of BEA (0.5 mg/kg) and KTC (0.5 mg/kg) prolonged survival of the host infected with Candida parapsilosis and reduced fungal colony counts in animal organs including kidneys, lungs, and brains. Such an effect was not achieved even with the high dose of 50 mg/kg KTC. These data support synergism between BEA and KTC and thereby a prospective strategy for antifungal therapy.
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