The impact of genomics on the search for novel tuberculosis drugs.

The emergence of multidrug-resistant strains of Mycobacterium tuberculosis has highlighted the need for new drugs to treat tuberculosis. Drugs that either shorten the overall duration of therapy or that simplify the regimen would significantly improve compliance and hence reduce treatment failure rates. The drug development process begins with identification and validation of specific targets. These may be relevant for inhibiting growth of the bacterium in vitro, and hence yield novel bactericidal agents, or they may be required at other stages of growth, such as survival in host macrophages. With the availability of the complete genome sequence of M. tuberculosis, the primary sequence of every drug target in the pathogen is known. A combination of approaches is being employed to exploit the information contained in the genome and thereafter to identify lead compounds that may yield new drugs.