Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/36624
Title: UNDERSTANDING RESPIRATORY MECHANISMS IN MYCOBACTERIA
Authors: AKUA BOATEMA OFORI-ANYINAM
Keywords: mycobacteria, Respiration, Mutants , Nutrient-starvation, Nutrient-rich, ROS
Issue Date: 28-Dec-2012
Source: AKUA BOATEMA OFORI-ANYINAM (2012-12-28). UNDERSTANDING RESPIRATORY MECHANISMS IN MYCOBACTERIA. ScholarBank@NUS Repository.
Abstract: Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), one of the major infectious diseases, affecting one-third of the world¿s population. Persistence of Mtb despite prolonged chemotherapy represents a major obstacle for the control of tuberculosis. Mtb is an obligate aerobe which has the ability to survive and persist for a long period of time even under hypoxic and nutrient starved conditions. The mechanisms employed by Mtb to persist in a quiescent state are largely unknown. Respiration is a major process through which Mtb generates ATP and intracellular concentration of ATP is significantly times lower in both hypoxic and nutrient starved non-replicating Mtb cells compared to aerobic replicating bacteria, making them exquisitely sensitive to any further depletion. Successful phase II studies using TMC207, an ATP synthase inhibitor and PA-824, a nitroimidazole, have clinically validated respiration as an important target , however, the respiratory mechanisms of Mycobacteria are poorly understood. A systematic approach using bioinformatic analysis and microbiological investigation using various mutants in respiratory pathway was carried out. Results obtained helped reveal the importance of these genes under nutrient starved conditions. Further mutations in respiratory pathway genes made the Mycobacteria exquisitely sensitive to bactericidal agents. A biochemical vesicle assay was also developed in order to carry out pathway based screens to identify novel compounds that could be used for treatment of tuberculosis. The current study has furthered our understanding of the respiratory physiology of aerobic growing and nutrient starved non- growing mycobacteria.
URI: http://scholarbank.nus.edu.sg/handle/10635/36624
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