Investigating the response of Mycobacterium tuberculosis to anti-tuberculosis drugs

Following the introduction of streptomycin in 1947, the main issue for new drug treatments has been to avoid drug resistance. This has been achieved, in part, by identifying the most effective drug combinations. Conventional methods used for testing combinations of current and new drug regimens and the response of M. tuberculosis to treatment are complicated and time consuming. Other issues include the need for accurate and early detection, drug resistance screening and follow-up measures to ensure treatment completion as intended. Thus, there is an urgent need to develop robust and rapid tools to assess drug efficacy and measure the response to treatment. The main scope of this thesis is to understand current available methods to predict the action of novel drugs in combination, and to determine drug responses to inform/improve patient management. Therefore, I evaluated the Molecular Bacterial Load (MBL) assay as a tool for diagnosis of M. tuberculosis and monitoring treatment response. This has confirmed that the MBL assay is a faster and more sensitive approach compared to culture-based methods. I then investigated the interaction between anti-tuberculosis drugs in vitro, and determined the transcriptomic ... (continues)