Disrupting Vital Protein Contacts in M Tuberculosis

The long term objective of this project is to develop a new class of drugs targeted to the disrupticontacts in the disease-causing microorganism Mycobacterium tuberculosis. The resurgence of tuberculworld and in the United States, particularly among those infected with HIV, emphasizes the need fordrugs. The specific aims of Phase I are to validate the two- hybrid interaction trap as an approachtuberculosis gene products and to use that system to identify interacting partners for use in drug sin Phase II. An interaction library of genomic M. tuberculosis DNA will be constructed in a yeast-E.a fusion to the activation domain of a transcriptional activator. Plasmids directing the expressiongenes fused to the DNA binding domain of a transcriptional activator will be constructed in anothervector. These baits, constructed from sequenced, essential M. tuberculosis genes will be used to screncoding fusion proteins which interact with the baits. The DNA sequence of library plasmid insertsproteins will be determined.