LY303366 Exhibits Rapid and Potent Fungicidal Activity in Flow Cytometric Assays of Yeast Viability
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LY303366 is a semisynthetic analog of the antifungal lipopeptide echinocandin B that inhibits (1,3)-β- d -glucan synthase and exhibits efficacy in animal models of human fungal infections. In this study, we utilized flow cytometric analysis of propidium iodide uptake, single-cell sorting, and standard microbiological plating methods to study the antifungal effect of LY303366 on Saccharomyces cerevisiae and Candida albicans . Our data indicate that an initial 5-min pulse treatment with LY303366 caused yeasts to take up propidium iodide and lose their ability to grow. Amphotericin B and cilofungin required longer exposure periods (30 and 180 min, respectively) and higher concentrations to elicit these fungicidal effects. These two measurements of fungicidal activity by LY303366 were highly correlated ( r > 0.99) in concentration response and time course experiments. As further validation, LY303366-treated yeasts that stained with propidium iodide were unable to grow in single-cell-sorted cultures. Our data indicate that LY303366 is potent and rapidly fungicidal for actively growing yeasts. The potency and rapid action of this new fungicidal compound suggest that LY303366 may be useful for antifungal therapy.
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Flow cytometry allows researchers to assess effects of selected compounds on thousands of individual cells within seconds.
“Flow cytometry provides unique advantages for studying antimicrobial activities, allowing researchers to assess the effects of selected compounds on thousands of individual cells within seconds [85].”
From Methods for screening and evaluation of antimicrobial activity: A review of protocols, advantages, and limitations (2024) · cites this paper as [85]
Many authors investigated the antibacterial and antifungal activities of many drugs using flow cytometry.
“Thus, many authors investigated the antibacterial and antifungal activities of many drugs using this methodology [95], [96], [97], [98].”
From Methods for in vitro evaluating antimicrobial activity: A review (2016) · cites this paper as [97]
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- Authors
- Green, L. J., Marder, P., Mann, L. L., Chio, L.-C., & Current, W. L.
- Affiliations
- Eli Lilly (United States) (US)
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 1999-04
- Volume
- 43
- Issue
- 4
- Pages
- 830-835
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC89213
- OpenAlex
- W2160355967
- Cited by
- 57
- References
- 0
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2021: 3 · 2020: 2 · 2016: 1 · 2015: 2 · 2014: 1 · 2012: 1
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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
- antifungal lipopeptides, fungicidal activity, Saccharomyces cerevisiae, Candida albicans, propidium iodide uptake, yeast viability, amphotericin B, antifungal therapy
- MeSH terms
- Anidulafungin, Antifungal Agents, Candida albicans, Cell Division, Cell Separation, Flow Cytometry, Humans, Indicators and Reagents, Microbial Sensitivity Tests, Peptides, Cyclic, Propidium, Saccharomyces cerevisiae, Time Factors, Echinocandins
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