Emergence of antibiotic-resistant microbial pathogens has created a medical crisis. Life-threatening bacterial pathogens, such as Staphylococcus aureus and Entercoccus faecalis, have developed widespread resistance to current antibiotics. Development of new antibiotics has been traditionally based on derivatizing known classes of compounds which target a limited number of cellular processes. Innovative technologies are needed to identify and develop novel antimicrobial agents for controlling antibiotic-resistant pathogens. In this Phase I proposal, the investigators propose to evaluate glutamyl-tRNA-gln amidotransferase, as a target for screening new lead compounds as potential antimicrobial agents. In several Gram-positive bacteria, this enzyme catalizes the formation of correctly aminoacylated tRNA-Gln by transfer of an amide group to the gamma-carboxylate of glutamyl-tRNA-Gln. In eukaryotic cells, the formation of glutaminyl-tRNA-Gln is catalyzed by glutamine-tRNA synthetase, providing the opportunity to develop chemotherapeutic agents specifically targeted at bacteria.
