GENETICS-ASSISTED TARGET EVALUATION IN ANTIBACTERIAL DRUG DISCOVERY

摘要

The present invention provides a method, which is designated GATE (Genetics- Assisted Target Evaluation), for gene analysis in pathogenic bacteria. GATE functionally classifies genes according to their essential or nonessential character with respect to bacterial growth or pathogenicity. The technology uses a nonessential scorable gene as an internal standard against which the dispensability of a given target gene is assessed by gene disruption by Campbell-type integration. Functional analysis was performed on 26 genes in the Gram-positive pathogen Streptococcus pyogenes. Application of this metho d resulted in a clear identification of essential and nonessential loci: 16 of the 26 genes evaluated in S. pyogenes clearly encoded functions essential fo r bacterial growth, while the remaining 10 encoded functions that were nonessential. The successful application of GATE has also been demonstrated in Staphylococcus aureus.