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Abstract
Tuberculosis (TB) in humans is the leading cause of death by a single infectious agent in the world today with approximately 2 billion individuals worldwide latently infected with the bacterium. Although the mortality rate for TB has been decreasing slowly in the last two decades, it still has not reached the levels set forth by the WHO End TB strategy. Currently, the most accepted method for eradication of disease is the Tuberculosis Directly Observed Treatment Shortcourse (TB-DOTS) program established by the WHO. Although this program has been finding and treating cases of active TB around the world, it is not a preventative method and therefore individuals with active disease may potentially pass on the disease before they have been diagnosed. Using Whole Genome Sequencing, Single Nucleotide Polymorphism analysis and examining transmission dynamics of TB in social networks outside of the home, we analyze the genome of clinical Mycobacterium tuberculosis (Mtb) isolates to determine transmission between individuals. We show that using a threshold of less than or equal to 12 SNPs as indicative of person-to-person transmission, clusters of transmission between individuals can be inferred. Incorporating this data with epidemiological data may provide a blueprint for the integration of public health interventions to prevent future TB transmission. In addition to transmission, TB latency is another major problem in the fight for eradication. During latency, individuals harboring the bacterium show no clinical symptoms and while dormant, the bacterium produces a dormancy protein called alpha-crystallin (Acr). Acr encompasses 25% of total proteins produced during hypoxia, however, not much is still understood about the mechanisms of the protein. The process by which Acr is transported outside of the cell is a major missing piece of the puzzle. Using constructed plasmids encoding different regions of the operon as well as determining the phosphorylation state of Acr, we further the understanding of the transport process. Altogether, this research will inform future research for the development of effective vaccines and antibiotics.