Finding the needle in the haystack

A new method for searching for antibiotics isolates compounds with inhibitory activity against more than one essential target.

Tudor Toma(
May 13, 2002

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 —...

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