Biomarkers of mycobacterial infection and disease, and molecular characterization of mycobacteria from high TB-burden countries.

Tuberculosis (TB) is a major public health problem throughout the world. Currently, there are 8 million new cases and 2-3 million deaths annually from TB. More than 95% of all cases and 98% of all deaths occur in developing countries, where few resources are available to ensure proper treatment. Despite significant strides in case detection and treatment, the incidence of TB continues to rise at an alarming rate in many countries. TB is a complex disease, characterized by a dynamic interaction between pat hogen and host that may lead to protection, disease or long-term persistent infection. Using microarray technology, initial host-specific immune responses to infection by Mycobacterium tuberculosis (Mtb) will be studied. In addition, the effect of variati ons of the cell wall components of the pathogen on host-response will be determined by studying the early global macrophage responses to in vitro infection with a wild-type and a mammalian cell entry protein (Mce)-mutant strain of Mtb. Sub-lineages of the Beijing lineage will be characterized to determine if particular genetic polymorphisms can be linked to the observed variations in the level of transmissability and increased frequency of drug resistance. In addition, by targeting selected markers specif ic for Th1/Th2-type immune responses, we aim to identify new markers of TB disease susceptibility and prognosis. Moreover, an elucidation of the frequency and clinical significance of non-tuberculous mycobacteria in a high TB-endemic area (South India) is important for both the accuracy of diagnostic endpoints and the immunogenicity of novel TB vaccines. The results from these studies can be translated into valuable information for improved prevention, early diagnosis and treatment of TB and can contribut e to building capacity (personally and locally) in the field of bioinformatics, molecular mycobacteriology and cellular immunology.