Pharmacological inhibition of host pathways enhances macrophage killing of intracellular bacterial pathogens

Human macrophages engulf bacteria into phagosomes, which then fuse with lysosomes to kill the bacteria. However, after engulfment, pathogenic bacteria such as <i>Mycobacterium tuberculosis</i>, <i>Legionella pneumophila</i>, and <i>Listeria monocytogenes</i> can block phagosome-lysosome fusion, allowing their survival. Here, we show that pharmacological inhibition of specific macrophage proteins reverses these effects and enhances bacterial killing. These findings suggest that targeting host factors involved in these processes may provide a therapeutic strategy to improve macrophage function against infections such as tuberculosis, Legionnaires' disease, and listeriosis.