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The Mycobacterium w Genome Program:
Complete Genome Sequencing and Genomics

    Mycobacterium w (M.w), is a cultivable, nonpathogenic and rapidly growing Mycobacterium classifiable in Runyon Group IV along with other rapid growers such as M. fortuitum, M. smegmatis, M. chelonae and M. vaccae on the basis of its growth and metabolic properties (Reddi et al., Int. J. Lepr. Other Mycobact. Dis. 1994, 62:229-36). This species of the genus Mycobacterium, interestingly, shares a number of common B and T cell determinants with Mycobacterium leprae and Mycobacterium tuberculosis (Zaheer et al., J. Infect. Dis. 1993, 167:401-10).

    Due to this fact, Mycobacterium w was used as the first, candidate leprosy vaccine strain. Immunotherapy with killed Mycobacterium w (M. w) vaccine was attempted in patients with borderline-lepromatous (BL), or lepromatous leprosy (LL) to determine whether immunization can hasten recovery and reduce the treatment time by invigorating cell-mediated immunity. Patients receiving the vaccine had rapid clinical improvement and was found to significantly reduce the bacterial burden (Zaheer et al., J. Infect. Dis. 1993, 167:401-10). A significant number of vaccinated patients demonstrated an upgrading in the histopathology of skin lesions. Rapid bacterial clearance was accompanied by distinct signs of clinical improvement in all such patients (Talwar et al., Vaccine. 1990, 8(2):121-9).

    This vaccine administered in various forms was initially developed at the National Institute of Immunology, New Delhi (India) and extensive clinical trials have been completed towards validation for field level testing. Copious data on immunotherapeutic significance of M. w emerged during clinical trials involving 80,000 subjects in India (India to sell leprosy vaccine. Asia Pacific Biotech News. 1998, 1 (30) pp 614). Following this, the Indian Government has already approved commercial level production of this theraputic vaccine and the technology was subsequently transferred to Cadila Pharmaceuticals in Ahmedabad, India.

    In view of the post genomic revelations on the mechanisms of mycobacterial pathogenesis and infection biology of tuberculosis, there is a need to revisit the biology of immunological cross reactivities between the M. leprae and M.w in a more effective manner. It is important to identify and characterize antigens of M.w that trigger T-cell responses in leprosy patients vaccinated with this organism and the mechanisms thereof (Yadava et al., Scand. J. Immunol. 1991 34:23-31) . For such studies, detailed knowledge of genome content, gene regulation, metabolic cascades, evolutionary genetics, antigenicity and survival mechanisms is required. These aspects of M.w are till now unexplored and it remains a largely unstudied bacillus at the genomic and proteomic levels, given few efforts on its molecular characterization by genotypic analyses of selected gene loci (Reddi et al., Int. J. Lepr. Other Mycobact. Dis. 1994, 62:229-36).

    Thus, there is a need for deciphering the biology of this bacillus by complete sequencing and analysis of its genome. Subsequent studies on comparative genomics (with M. tuberculosis, M. bovis, M. bovis BCG, M. leprae and M. avium) and biology components of the study will enhance our knowledge about possible mechanisms involved in its clearance in leprosy patients and efficacy as a vaccine candidate for leprosy and other mycobacterial diseases. This will also help in generating useful data on evolution of mycobacterial genome and the mysterious phenomenon of genomic downsizing (as seen in M. leprae and M. tuberculosis, M. bovis, and possibly in M. w. as well).

    In view of this, DBT has supported a project on "The Mycobacterium w Genome Program: Complete Genome Sequencing and Genomics".