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Antifungal Chemical Compounds Identified Using a C. elegans Pathogenicity Assay
 

Summary: Antifungal Chemical Compounds Identified
Using a C. elegans Pathogenicity Assay
Julia Breger1
, Beth Burgwyn Fuchs1
, George Aperis1
, Terence I. Moy2
, Frederick M. Ausubel2,3
, Eleftherios Mylonakis1*
1 Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America, 2 Department of Molecular Biology, Massachusetts
General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 3 Department of Genetics, Harvard Medical School, Boston, Massachusetts,
United States of America
There 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.

  

Source: Ausubel, Frederick M. - Department of Genetics, Harvard University

 

Collections: Biology and Medicine