High-throughput screen for novel antimicrobials using a whole animal infection model.
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.
Moy
Terence I
TI
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Conery
Annie L
AL
Larkins-Ford
Jonah
J
Wu
Gang
G
Mazitschek
Ralph
R
Casadei
Gabriele
G
Lewis
Kim
K
Carpenter
Anne E
AE
Ausubel
Frederick M
FM
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000382:microbiology*; D020650:Combinatorial Chemistry Techniques; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000254:growth & development; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy; D006801:Humans; D015394:Molecular Structure
D000900:Anti-Bacterial Agents