Cited by 120Antifungal resistance and susceptibilityBacterial biofilms and quorum sensingFungal and yeast genetics research

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High-Throughput Screening of a Collection of Known Pharmacologically Active Small Compounds for Identification of Candida albicans Biofilm Inhibitors

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Siles, Samuel A., Srinivasan, Anand, Pierce, Christopher G., Lopez-Ribot, José L., Ramasubramanian, Anand K.·2013·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.00680-13PMC PMC3719724

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Abstract

Candida albicans is the most common etiologic agent of systemic fungal infections with unacceptably high mortality rates. The existing arsenal of antifungal drugs is very limited and is particularly ineffective against C. albicans biofilms. To address the unmet need for novel antifungals, particularly those active against biofilms, we have screened a small molecule library consisting of 1,200 off-patent drugs already approved by the Food and Drug Administration (FDA), the Prestwick Chemical Library, to identify inhibitors of C. albicans biofilm formation. According to their pharmacological applications that are currently known, we classified these bioactive compounds as antifungal drugs, as antimicrobials/antiseptics, or as miscellaneous drugs, which we considered to be drugs with no previously characterized antifungal activity. Using a 96-well microtiter plate-based high-content screening assay, we identified 38 pharmacologically active agents that inhibit C. albicans biofilm formation. These drugs were subsequently tested for their potency and efficacy against preformed biofilms, and we identified three drugs with novel antifungal activity. Thus, repurposing FDA-approved drugs opens up a valuable new avenue for identification and potentially rapid development of antifungal agents, which are urgently needed.

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Authors: Siles, S. A., Srinivasan, A., Pierce, C. G., Lopez-Ribot, J. L., & Ramasubramanian, A. K.
Affiliations: The University of Texas at San Antonio (US)
Departments of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA
ORCID: Pierce, Christopher G.
Ramasubramanian, Anand K.
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2013-08
Volume: 57
Issue: 8
Pages: 3681-3687
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.00680-13
PMC: PMC3719724
OpenAlex: W2171146043
Cited by: 120
References: 47
Citations by year: 2026: 4 · 2025: 5 · 2024: 5 · 2023: 10 · 2022: 11 · 2021: 10 · 2020: 16 · 2019: 10 · 2018: 14 · 2017: 6 · 2016: 9 · 2015: 14 · 2014: 3 · 2013: 2
FWCI: 6.78
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Defense
San Antonio Area Foundation
National Heart, Lung, and Blood Institute (SC1HL112629)
National Institute of Dental and Craniofacial Research (R01DE023510)
Army Research Office
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords: Candida albicans, biofilm formation, antibiofilm agents, antifungal drug repurposing, FDA-approved drugs, Prestwick Chemical Library, high-content screening, drug discovery, systemic fungal infection
MeSH terms: Amphotericin B, Antifungal Agents, Benzethonium, Candida albicans, Dimethyl Sulfoxide, Disinfectants, Dose-Response Relationship, Drug, Microbial Sensitivity Tests, Biofilms, Microbial Viability, Small Molecule Libraries, High-Throughput Screening Assays

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High-Throughput Screening of a Collection of Known Pharmacologically Active Small Compounds for Identification of Candida albicans Biofilm Inhibitors

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