Finding the needle in the haystack

Current techniques for identifying novel antibiotics are based on broad cell-based screenings of antibacterial molecules, but these methods do not reveal the biochemical target of a lead compound. In May Nature Biotechnology, Joseph DeVito and colleagues from Bristol-Myers Squibb Company describe a new array of target-specific screening strains of Escherichia coli that can identify antibiotic compounds with good inhibitory activity against more than one essential target (Nat Biotechnol 2002, 20:478-483).

DeVito et al. used recombination systems derived from the bacteriophages λ and P1 to engineer nine strains of E. coli for low-level expression of a single, essential gene product, thus making each strain hypersusceptible to specific inhibitors of that gene target. They observed that screening the strains from the array in parallel against a large chemical library permitted identification of new inhibitors of bacterial growth. Compounds identified in this way — such as MurA inhibitors — were also found to ...