Tuberculosis (TB) is one of the leading causes of death from a single infectious agent (Mycobacterium tuberculosis), second only to Coronavirus disease 2019 (COVID-19). The emergence of drug resistant strains, the variable efficacy of the BCG vaccination worldwide and the vulnerability of immunocompromised individuals infected with Human immunodeficiency virus suffering from acquired immune deficiency syndrome (HIV/AIDS) has prompted the scientific community to develop new strategies towards the development of novel anti-tubercular drugs, vaccine candidates and treatment strategies. The genus Mycobacterium has an elaborate and highly impermeable cell envelope, with additional molecular decorations contributing to its virulence and pathogenesis. Presence of this highly evolved cell envelope adds additional complexities in its treatment strategies, with the ongoing global pandemic exacerbating the situation, with tuberculosis claiming 1.5 million lives in 2020.
An understanding of mycobacterial cell wall assembly and host pathogen interactions are key aspects to tackle this disease. This thesis addresses these aspects in two separate projects with an overall aim to advance research on TB; and aid in the development of novel anti-tubercular therapeutics. Firstly, an essential enzyme involved in mycobacterial cell wall assembly has been characterised for its role in growth, biofilm formation and pathogenesis of M. bovis BCG - the vaccine strain of TB. Secondly, a host immune response regulator protein which was reported to encourage intracellular mycobacterial growth and proliferation has been studied to contributing to research on the development of host directed therapies to combat tuberculosis
