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

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 scre...

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Main Authors: Ikechukwu Okoli, Jeffrey J Coleman, Emmanouil Tampakakis, W Frank An, Edward Holson, Florence Wagner, Annie L Conery, Jonah Larkins-Ford, Gang Wu, Andy Stern, Frederick M Ausubel, Eleftherios Mylonakis
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-09-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2737148?pdf=render
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author Ikechukwu Okoli
Jeffrey J Coleman
Emmanouil Tampakakis
W Frank An
Edward Holson
Florence Wagner
Annie L Conery
Jonah Larkins-Ford
Gang Wu
Andy Stern
Frederick M Ausubel
Eleftherios Mylonakis
author_facet Ikechukwu Okoli
Jeffrey J Coleman
Emmanouil Tampakakis
W Frank An
Edward Holson
Florence Wagner
Annie L Conery
Jonah Larkins-Ford
Gang Wu
Andy Stern
Frederick M Ausubel
Eleftherios Mylonakis
author_sort Ikechukwu Okoli
collection DOAJ
description 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.
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spelling doaj.art-c46985386a7e47d58142318cc83e1ed12022-12-21T23:27:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-09-0149e702510.1371/journal.pone.0007025Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.Ikechukwu OkoliJeffrey J ColemanEmmanouil TampakakisW Frank AnEdward HolsonFlorence WagnerAnnie L ConeryJonah Larkins-FordGang WuAndy SternFrederick M AusubelEleftherios MylonakisCandida 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.http://europepmc.org/articles/PMC2737148?pdf=render
spellingShingle Ikechukwu Okoli
Jeffrey J Coleman
Emmanouil Tampakakis
W Frank An
Edward Holson
Florence Wagner
Annie L Conery
Jonah Larkins-Ford
Gang Wu
Andy Stern
Frederick M Ausubel
Eleftherios Mylonakis
Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.
PLoS ONE
title Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.
title_full Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.
title_fullStr Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.
title_full_unstemmed Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.
title_short Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.
title_sort identification of antifungal compounds active against candida albicans using an improved high throughput caenorhabditis elegans assay
url http://europepmc.org/articles/PMC2737148?pdf=render
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