4) Pathogenesis and Lessons from Leprosy
Chair： Dr. J. Colston
Scientifically, the opportunities for studying pathogenesis in leprosy could not be more timely. The availability of the complete sequence of the M. tuberculosis genome and the considerable inroads that have been made in to sequencing the M. leprae genome, mean that we will be able to identify genes associated with particular biological properties by sequence comparison. Techniques for genetic exchange between mycobacteria will make it possible to test for gene functions in a way which is not possible with the noncultivable M. leprae. Additionally, novel approaches for developing new animal models (gene knockout and transgenic animals) developing at a rapid pace; these will prove invaluable for testing hypotheses relating to control of infection and immunopathological mechanisms.
We believe that it is important to continue to address questions of pathogenesis for two broad reasons. Leprosy is a paradigm for intracellular infections. Comparative pathogenesis studies will provide important information for understanding leprosy, but infectious processes in general. There are many important lessons that can be learned from the study of leprosy. Secondly, the consequences of the host-pathogen interaction remain a clinical problem for the leprosy patient for many years after bacteriological cure has been achieved. Rapid advances have been made in the pharmaceutical and technological fields for developing novel approaches to such things as wound healing, the treatment of immunopathological conditions, and other infections. However, these industries are not interested in leprosy and it will be up to us to exploit the developments for the treatment of leprosy patients. An understanding of the mechanisms involved in leprosy will enable us to make informed decisions as to which are likely to be useful for the leprosy patient.
We would regard the following as priority areas：
1. Completion of the genome sequencing project and comparative genomics with related organisms. This will enable us to understand what is biologically unique about M. leprae and hence to provide clues for the molecular basis of its pathogenicity.
2. Proteomic analysis, which will complement the genomic approach, will help us to understand which proteins are important for survival within the infected host. Once these proteins have been identified, further genetic studies can be undertaken.
3. New animal models, including transgenic and knockout mice, will play an important role in exploring pathogenesis. For example, mice with specific immunological deficiencies will enable us to determine important pathways in host immunity. These studies require highly specialized facilities and expertise, such as those available in mouse foot pad laboratories, which are in danger of being lost; in order to exploit these new models, it is important that these be maintained.
4. Molecular approaches to characterizing the interaction between M. leprae and the schwann cell will enable us to further understand the unique pathogenic mechanism of M. Ieprae, and will complement clinical studies on nerve damage.
