title: Bugs, drugs and chemical genomics.
abstract: The serendipitous discovery of penicillin inspired intensive research into how small molecules affect basic cellular processes and their potential to treat disease. Biochemical and genetic approaches have been fundamental for clarifying small-molecule modes of action. Genomic technologies have permitted the use of chemical-genetic strategies that comprehensively study compound-target relationships in the context of a living cell, providing a systems biology view of both the cellular targets and the interdependent networks that respond to chemical stress. These studies highlight the fact that in vitro determinations of mechanism rarely translate into a complete understanding of drug behavior in the cell. Here, we review key discoveries that gave rise to the field of chemical genetics, with particular attention to chemical-genetic strategies developed for bakers' yeast, their extension to clinically relevant microbial pathogens, and the potential of these approaches to affect antimicrobial drug discovery.
authors.affiliation: Department of Infectious Disease, Merck, Kenilworth, New Jersey, USA. terry_roemer@merck.com
authors.forename: Terry
authors.initials: T
authors.lastname: Roemer
authors.forename: Julian
authors.initials: J
authors.lastname: Davies
authors.forename: Guri
authors.initials: G
authors.lastname: Giaever
authors.forename: Corey
authors.initials: C
authors.lastname: Nislow
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery; D023281:Genomics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D000900:Anti-Bacterial Agents