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High-Throughput Screen for Novel Antimicrobials using a Whole Animal Infection Model

  作者 MOY TERENCE I; CONERY ANNIE L; LARKINSFORD JONAH; WU GANG; MAZITSCHEK RALPH; CASADEI GABRIELE; LEWIS KIM; CARPENTER ANNE E; AUSUBEL FREDERICK M  
  选自 期刊  ACS CHEMICAL BIOLOGY;  卷期  2009年4-7;  页码  527-533  
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[摘要]The nematode Coenorhabditis elegons is a unique whole animal model system for identifying small molecules with in vivo anti-infective properties. C elegons can be infected with a broad range of human pathogens, including Enterococcus faecalis, an important human nosocomial pathogen. Here, we describe an automated, high-throughput screen of 37,200 compounds and natural product extracts for those that enhance survival of C elegans infected with E faecalis. Using a robot to dispense live, infected animals into 384-well plates and automated microscopy and image analysis, we identified 28 compounds and extracts not previously reported to have antimicrobial properties, including six structural classes that cure infected C elegons animals but do not affect the growth of the pathogen in vitro, thus acting by a mechanism of action distinct from antibiotics currently in clinical use.

 
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