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PLoS One DOI:10.1371/journal.pone.0007025

Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.

Publication TypeJournal Article
Year of Publication2009
AuthorsOkoli, I, Coleman, JJ, Tampakakis, E, Tempakakis, E, W An, F, Holson, E, Wagner, F, Conery, AL, Larkins-Ford, J, Wu, G, Stern, A, Ausubel, FM, Mylonakis, E
JournalPLoS One
Volume4
Issue9
Pagese7025
Date Published2009 Sep 14
ISSN1932-6203
KeywordsAnimals, Antifungal Agents, Caenorhabditis elegans, Candida albicans, Chemistry, Pharmaceutical, Combinatorial Chemistry Techniques, Drug Design, Drug Discovery, Drug Evaluation, Preclinical, Immunosuppressive Agents, Microbial Sensitivity Tests, Mutation
Abstract

Candida albicans, the most common human pathogenic fungus, can establish a persistent lethal infection in the intestine of the microscopic nematode Caenorhabditis elegans. The C. elegans-C. albicans infection model was previously adapted to screen for antifungal compounds. Modifications to this screen have been made to facilitate a high-throughput assay including co-inoculation of nematodes with C. albicans and instrumentation allowing precise dispensing of worms into assay wells, eliminating two labor-intensive steps. This high-throughput method was utilized to screen a library of 3,228 compounds represented by 1,948 bioactive compounds and 1,280 small molecules derived via diversity-oriented synthesis. Nineteen compounds were identified that conferred an increase in C. elegans survival, including most known antifungal compounds within the chemical library. In addition to seven clinically used antifungal compounds, twelve compounds were identified which are not primarily used as antifungal agents, including three immunosuppressive drugs. This assay also allowed the assessment of the relative minimal inhibitory concentration, the effective concentration in vivo, and the toxicity of the compound in a single assay.

DOI10.1371/journal.pone.0007025
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/19750012?dopt=Abstract

Alternate JournalPLoS ONE
PubMed ID19750012
PubMed Central IDPMC2737148
Grant ListR01 AI075286 / AI / NIAID NIH HHS / United States
T32 AI007061 / AI / NIAID NIH HHS / United States
P30 DK040561 / DK / NIDDK NIH HHS / United States
P30 DK040561-14 / DK / NIDDK NIH HHS / United States
R01 AI072508 / AI / NIAID NIH HHS / United States
N01CO12400 / CA / NCI NIH HHS / United States
N01-CO-12400 / CO / NCI NIH HHS / United States