Show simple item record

dc.contributor.authorBreger, Julia
dc.contributor.authorFuchs, Beth Burgwyn
dc.contributor.authorAperis, George
dc.contributor.authorMoy, Terence I
dc.contributor.authorAusubel, Frederick M.
dc.contributor.authorMylonakis, Eleftherios
dc.contributor.authorCormack, Brendan P
dc.date.accessioned2010-10-28T14:35:40Z
dc.date.issued2007
dc.identifier.citationBreger, Julia, Beth Burgwyn Fuchs, George Aperis, Terence I. Moy, Frederick M. Ausubel, Eleftherios Mylonakis, and Brendan P. Cormack. 2007. Antifungal Chemical Compounds Identified Using a Pathogenicity Assay. PLoS Pathogens 3:e18.en_US
dc.identifier.issn1553-7366en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4513032
dc.description.abstractThere is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans intestinal track. Importantly, key components of Candida pathogenesis in mammals, such as filament formation, are also involved in nematode killing. We devised a Candida-mediated C. elegans assay that allows high-throughput in vivo screening of chemical libraries for antifungal activities, while synchronously screening against toxic compounds. The assay is performed in liquid media using standard 96-well plate technology and allows the study of C. albicans in non-planktonic form. A screen of 1,266 compounds with known pharmaceutical activities identified 15 (∼1.2%) that prolonged survival of C. albicans-infected nematodes and inhibited in vivo filamentation of C. albicans. Two compounds identified in the screen, caffeic acid phenethyl ester, a major active component of honeybee propolis, and the fluoroquinolone agent enoxacin exhibited antifungal activity in a murine model of candidiasis. The whole-animal C. elegans assay may help to study the molecular basis of C. albicans pathogenesis and identify antifungal compounds that most likely would not be identified by in vitro screens that target fungal growth. Compounds identified in the screen that affect the virulence of Candida in vivo can potentially be used as “probe compounds” and may have antifungal activity against other fungi.en_US
dc.description.sponsorshipMolecular and Cellular Biologyen_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.ppat.0030018en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1790726/pdf/en_US
dash.licenseLAA
dc.subjectCaenorhabditisen_US
dc.subjectinfectious diseasesen_US
dc.subjectmicrobiologyen_US
dc.subjectyeast and fungien_US
dc.subjectMus (mouse)en_US
dc.subjectin vitroen_US
dc.titleAntifungal Chemical Compounds Identified Using a C. elegans Pathogenicity Assayen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Pathogensen_US
dash.depositing.authorAusubel, Frederick M.
dc.date.available2010-10-28T14:35:40Z
dc.identifier.doi10.1371/journal.ppat.0030018*
dash.contributor.affiliatedAusubel, Frederick
dash.contributor.affiliatedMylonakis, E


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record