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Exploring the use of calcium channel blockers to potentiate the effect of second-line drugs in Mycobacterium bovis BCG-infected human macrophages with minimal toxicity.

Mycobacterium tuberculosis is the bacteria responsible for causing Tuberculosis in humans. Tuberculosis (TB) is responsible for a huge number of deaths every year and its treatment usually involve a complex course of antibiotics. The first line drugs used to treat TB not always work and in multidrug resistant cases there is the need to use more potent antibiotics that we called second-line drugs. These second-line drugs are usually more toxic to the patient and much more expensive. If we can decrease the concentration of these drugs, we can avoid issues such as toxicity. For that, we can develop an adjuvant therapy, which involves combining antibiotics with calcium channel blockers. The effect of these combinations will be tested on human infected immune cells known as macrophages. Macrophages are cells of the immune system that engulf or ‘swallow’ the pathogenic bacterium M. bovis. These are important cells to help on fighting the infection. Although calcium channel blockers are not antibiotics, they seem to boost the macrophage ability to kill the internalised bacteria. This project will investigate how calcium channel blockers can be used together with second line drugs to treat M. tuberculosis. In this project, M. bovis BCG (the bacterial strain used for the TB vaccine) will be used as a model for TB. Results from this project will help us identify effective combinations of drugs that could be used to treat TB patients with minimal toxicity and avoid further development of resistance to antibiotics.