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

被引：159

作者：

Moy, Terence I. ^{[1
,2
,3
]}

Conery, Annie L. ^{[2
,3
]}

Larkins-Ford, Jonah ^{[2
,3
]}

Wu, Gang ^{[2
,3
]}

Mazitschek, Ralph ^{[4
]}

Casadei, Gabriele ^{[5
]}

Lewis, Kim ^{[5
]}

Carpenter, Anne E. ^{[6
]}

Ausubel, Frederick M. ^{[1
,2
,3
]}

机构：

[1] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[2] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA

[5] Northeastern Univ, Dept Biol, Boston, MA 02115 USA

[6] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

来源：

ACS CHEMICAL BIOLOGY | 2009年 / 4卷 / 07期

关键词：

ANTIBACTERIAL DRUG DISCOVERY; CAENORHABDITIS-ELEGANS; C-ELEGANS; INHIBITORS; BACTERIAL; ASSAY;

D O I：

10.1021/cb900084v

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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.

引用

页码：527 / 533

页数：7

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