Faculty of Science
Microbiology and Immunology

Comparative phenotypic screening identifies protein synthesis inhibitors as compounds that enhance early acidification of Mycobacterium tuberculosis in macrophages

schematic of phagosome acidification assay

Publication Date

Publication Journal

ACS Infectious Diseases

Author(s)

Leah Rankine-Wilson and Yossef Av-Gay

Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, is taken up by macrophage immune cells that trap it within a membrane bubble known as a phagosome. Macrophages can acidify the phagosome in an attempt to kill and degrade the invading pathogen. However, Mtb actively blocks this acidic stress. To provide a tool that can be used to better understand these dynamics, the authors developed an assay that measures acidification in infected macrophages and correlates this to infection outcome. They screened libraries of compounds and found that compounds that interfere with bacterial protein and DNA synthesis enhanced early acidification of the phagosomes. This work establishes a valuable platform for investigating Mtb survival mechanisms and accelerating the development of improved therapeutics for tuberculosis. 

  • Av-Gay Lab

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Microbiology and Immunology

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