identification of antifungal compounds active against candida albicans using an improved high-throughput caenorhabditis elegans assay识别抗真菌化合物的活性对白色念珠菌使用一种改进的高通量线虫试验.pdfVIP

Identification of Antifungal Compounds Active against Candida albicans Using an Improved High-Throughput Caenorhabditis elegans Assay 1 1 1 2 2 Ikechukwu Okoli , Jeffrey J. Coleman , Emmanouil Tempakakis , W. Frank An , Edward Holson , 2 3 3 3 2 Florence Wagner , Annie L. Conery , Jonah Larkins-Ford , Gang Wu , Andy Stern , Frederick M. 3 1 Ausubel , Eleftherios Mylonakis * 1 Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America, 2 Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, United States of America, 3 Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America 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 kn