Novel Drug Development Strategy for M Tuberculosis

Mycobacterium tuberculosis is a leading cause of death by infectious disease in the third world andincreasing in the United States, primarily because of the AIDS epidemic. Strains of M. tuberculosisresistant to the many anti-tuberculosis drugs, including isoniazid and rifampicin. Cubist Pharmaceutaminoacyl-tRNA syntheses, an essential family of enzymes involved in protein synthesis, to develop aantibiotics. The tRNA syntheses have significantly diverged through evolution, leading to distinct svariabilities which facilitate rational drug design for species-specific inhibition. Our research wisystems for cloned and expressed M. tuberculosis tRNA synthetase genes via enzyme and whole cell asstuberculosis genes will be expressed in bacterial and/or yeast null strains which lack the appropriaexpression systems will serve as convenient test strains to screen small molecules for potential druinhibitors can be subsequently screened for specificity against a parallel test strain for human tRNDiscrimination of human and M. tuberculosis tRNA synthetases will yield a powerful drug candidate focontrol of TB.