Tuberculosis control in animals and humans alike requires early detection of Mycobacterium tuberculosis complex as well as current knowledge about the transmission patterns of the disease in the respective populations. These two building blocks provide the foundation on which the disease control programs can build their policies to expediate control efforts. In this thesis we amalgamate molecular epidemiology, genomics, and proteomics. We studied the transmission pattern of M. tuberculosis and its evolution within a marginalized population. The patterns led to the identification of gaps in TB control policies in marginalized populations with little access to healthcare. Similarly, we studied the genomewide polymorphisms in a naturally attenuated strain - M. bovis strain Ravenel to elucidate possible mechanisms for its reduced virulence and pathogenicity. Insights gained from genome sequence analysis in conjunction with pathogenesis study for M. bovis Ravenel paved the pathway to defining the complex and multi-faceted reasons for attenuation of the oldest bacteria of the world. Next, pathogen-specific biomarkers were evaluated to assist in unambiguous disease detection across multiple host species. Discovery and validation of biomarkers work facilitated the field diagnostic applications for TB in animals and humans. This three-pronged approach developed in this study, understanding the genomic basis of attenuation, and enhanced field TB diagnostics in the animal-human interface.
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