Seminar: Leveraging Macrophage Vacuolar Acidification for Tuberculosis Drug Discovery

Abstract: Treatment for tuberculosis is failing, necessitating new drug discovery strategies against Mycobacterium tuberculosis (Mtb). This obligate human pathogen survives in alveolar macrophages and inhibits phagosome acidification. Antithetically, we show chemical inhibition of vacuolar ATPase impedes Mtb's intracellular growth. This led to the question: Can phagosome acidification indicate Mtb viability in drug screening assays? I developed a rapid, high-content tool to monitor phagosome acidification as a potential surrogate marker for Mtb intracellular viability in macrophages. Through a comparative screening campaign, I investigated the correlation between drug classes and early phagosome acidification. This work illustrates the complex relationship between phagosome acidification and Mtb intracellular growth, offering new insights for TB drug discovery.