Studies are proposed that will lead to an understanding of the genes and gene products of Mycobacterium leprae that are important in the pathogenicity of this organism through molecular and functional analyses of recombinant molecules from genomic libraries. Detailed taxonomic and strain diversity studies will be undertaken initially as well as studies to provide information concerning the existence of an animal reservoir. This information is essential for developing means for accurate diagnosis and prevention (by Immunization) of leprosy. Specifically, we will: (1) employ DNA restriction fragment length polymorphism analyses to (a) assess relatedness among the genomes of M. leprae infecting humans, cultivable acid-fast bacteria obtained from leprosy patients, non-cultivable mycobacteria obtained from animals (armadillos, Mangabey monkeys, chimpanzees) with leprosy-like disease and cultivable mycobacteria isolated from soil and (b) assess relatedness or divergence in the genomes of M. leprae strains isolated from leprosy patients in different parts of the world. (2) identify and analyze genes specifying enzymes that might contribute to the ability of M. leprae to destroy connective tissue and/or to attach to, invade and multiply in nerves. The research will be done in conformance with the NIH Guidelines for Recombinant DNA Research. The studies will make use of the technologies of molecular genetics bacterial genetics, microbiology, immunology and biochemistry.
