ASSAYS FOR INHIBITORS OF BACTERIAL TRANSLATION INITIATION FACTOR 3

摘要

The invention is directed to a high-throughput screening system for identifying new antibacterial agents specifically targeted against an essential component of the bacterial translation apparatus, IF3. The assay uses a reporter gene system in whole cells, and is based on the ability of IF3 to discriminate against translation initiation at the atypical start codon of the reporter gene. The figure is a schematic diagram of the pAUU-CAT reporter gene construct in which the CAT gene has its ATG initiator codon replaced with ATT. Inhibitors of IF3 are expected to result in increased growth of specially-designed test cells due to higher levels of expression from the reporter gene. The invention further provides secondary assays which are used to further study the test compounds which produced positive results in the screening assays of the invention. The invention also encompasses reporter gene constructs, test cells, and compounds identified by the methods of the invention.