A High-Throughput Screening Assay for Fungicidal Compounds against Cryptococcus neoformans
Open accessAbstract
Cryptococcus neoformans is a pathogenic fungus that causes meningitis worldwide, particularly in human immunodeficiency virus (HIV)-infected individuals. Although amphotericin B is the "gold standard" treatment for cryptococcal meningitis, the toxicity and inconvenience of intravenous injection emphasize a need for development of new anticryptocccal drugs. Recent data from humans and animal studies suggested that a nutrient-deprived host environment may exist in cryptococcal meningitis. Thus, a screening assay for identifying fungicidal compounds under nutrient-deprived conditions may provide an alternative strategy to develop new anticryptococcal drugs for this disease. A high-throughput fungicidal assay was developed using a profluorescent dye, alamarBlue, to detect residual metabolic activity of C. neoformans under nutrient-limiting conditions. Screening the Library of Pharmacologically Active Compounds (LOPAC) with this assay identified a potential chemical scaffold, 10058-F4, that exhibited fungicidal activity in the low micromolar range. These results thus demonstrate the feasibility of this alamarBlue-based assay for high-throughput screening of fungicidal compounds under nutrient-limiting conditions for new anticryptococcal drug development.
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Alternative high-throughput screening platforms that specifically identify fungicidal molecules have been developed.
“In addition to employing non-traditional compound libraries for the discovery of novel antifungals, alternative high-throughput screening platforms that specifically identify fungicidal molecules have been developed91,92.”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [92]
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- Authors
- Rabjohns, J. L. A., Park, Y.-D., Dehdashti, J., Sun, W., Henderson, C., Zelazny, A., Metallo, S. J., Zheng, W., & Williamson, P. R.
- Affiliations
- National Institutes of Health (US)
- Georgetown University (US)
- Corresponding author
- Williamson, Peter R.
- Venue
- SLAS Discovery
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 19
- Issue
- 2
- Pages
- 270-277
- ISSN
- 2472-5552 (ISSN-L)
- PMC
- PMC4017337
- OpenAlex
- W2165805587
- Cited by
- 33
- References
- 30
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 1 · 2019: 3 · 2018: 3 · 2016: 6 · 2015: 2 · 2014: 2 · 2013: 4
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- SLAS DISCOVERY (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (ZIBTR000004, Z99 AI999999)
- National Institute of Allergy and Infectious Diseases (ZIAAI001123, ZIAAI001124)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- Cryptococcus neoformans, cryptococcal meningitis, high-throughput screening, fungicides, nutrient deprivation, Alamar Blue, 10058-F4, antifungal drug development, HIV-associated cryptococcosis
- MeSH terms
- Amphotericin B, Antifungal Agents, Cryptococcus neoformans, Humans, Thiazoles, Meningitis, Cryptococcal, Small Molecule Libraries, High-Throughput Screening Assays
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