Format

Send to

Choose Destination
Nat Chem Biol. 2013 Apr;9(4):222-31. doi: 10.1038/nchembio.1205.

Systems-level antimicrobial drug and drug synergy discovery.

Author information

1
Infectious Disease Research, Merck Research Laboratories, Kenilworth, New Jersey, USA. terry_roemer@merck.com

Abstract

Here, we review the 'target-centric' genomic strategy to antimicrobial discovery and share our perspective on identification, validation and prioritization of potential antimicrobial drug targets in the context of emerging chemical biology, genomics and phenotypic screening strategies. We propose that coupling the dual processes of antimicrobial small-molecule screening and target identification in a whole-cell context is essential to empirically annotate 'druggable' targets and advance early stage antimicrobial discovery. We also advocate a systems-level approach to annotating synthetic-lethal genetic interactions comprehensively within yeast and bacteria models. The resulting genetic interaction networks provide a landscape to rationally predict and exploit drug synergy between cognate inhibitors. We posit that synergistic combination agents provide an important and largely unexploited strategy to 'repurpose' existing chemical space and simultaneously address issues of potency, spectrum, toxicity and drug resistance in early stages of antimicrobial drug discovery.

PMID:
23508188
DOI:
10.1038/nchembio.1205
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center