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Updated: Apr 4, 2026

High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method
Published on: May 21, 2018
Cryptic antifungal compounds active by synergism with polyene antibiotics
Hiroshi Kinoshita1, Mariko Yoshioka1, Fumio Ihara2
1International Center for Biotechnology, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
This study enhanced fungal cell membrane permeability using nystatin, revealing new antifungal compounds helvolic acid and terramide A from entomopathogenic fungi. This method effectively screens for novel antifungal activities.
Area of Science:
- Microbiology
- Mycology
- Pharmacology
Background:
- Most antifungal compounds target fungal cell walls or membranes, limiting the efficacy of other antibiotics due to poor cell penetration.
- Enhancing fungal cell membrane permeability could unlock the antifungal potential of numerous existing antibiotic compounds.
Purpose of the Study:
- To investigate if enhancing fungal cell membrane permeability with nystatin can reveal novel antifungal activities from microbial sources.
- To identify and characterize new antifungal compounds from entomopathogenic fungi using a permeability-enhanced screening approach.
Main Methods:
- Utilized the polyene antibiotic nystatin to create pores in fungal cell membranes, increasing cellular permeability.
- Screened culture extracts from entomopathogenic fungi for antifungal activity in the presence of nystatin.
- Purified and identified active antifungal components from positive extracts using chromatographic and spectroscopic techniques.
Main Results:
- Nystatin treatment significantly enhanced the cellular permeability of fungi.
- Several entomopathogenic fungal extracts exhibited antifungal activity when combined with nystatin.
- Helvolic acid and terramide A were identified as potent antifungal compounds, with their minimum inhibitory concentrations reduced four-fold by nystatin.
Conclusions:
- The developed screening method, utilizing nystatin to enhance cell permeability, is effective for discovering novel antifungal compounds.
- Helvolic acid and terramide A represent promising candidates for new antifungal therapies.
- Targeting fungal cell membrane permeability offers a viable strategy to broaden the spectrum of antifungal drug discovery.
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