High-throughput Screen for Novel Antimicrobials Using a Whole Animal Infection Model

Overview

Journal ACS Chem Biol

Publisher American Chemical Society

Specialties Biochemistry
Biology

Date 2009 Jul 4

PMID 19572548

Citations 106

Authors

Terence I Moy

Annie L Conery

Jonah Larkins-Ford

Gang Wu

Ralph Mazitschek

Gabriele Casadei

Kim Lewis

Anne E Carpenter

Frederick M Ausubel

Affiliations

Soon will be listed here.

Abstract

The nematode Caenorhabditis elegans is a unique whole animal model system for identifying small molecules with in vivo anti-infective properties. C. elegans 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. elegans 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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