Mycobacterial species are the causative agents of several important human diseases; the most devastating of these diseases are tuberculosis, leprosy, and opportunistic Mycobacterium avium infections of patients with Human Immunodeficiency Virus (HIV). Very little is known about gene regulation in mycobacteria. Indeed, only as recently as 1987 were scientists able to introduce DNA into mycobacteria; this was an important first step for applying molecular biological techniques to these organisms. In particular, mycobacterial promoters have not been analyzed in detail and there are no well characterized transcriptional regulatory systems in mycobacteria. Understanding gene regulation in mycobacteria is important because it may reveal aspects of the pathogenesis of these organisms and provide the basis for the development of antimycobacterial drugs, better diagnostic tools, and improved vaccines. Mycobacteriophage L5 is a well-characterized temperate phage of M. smegmatis. Previous genetic studies suggest that gene 71 of L5 encodes a repressor protein required for the maintenance of lysogeny. The studies in this proposal will explore the mechanism of transcriptional regulation by gp7l, establish a system for regulated gene expression in mycobacteria, and assist in the construction of recombinant BCG vaccines.
