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

ABSTRACT: After ingestion into macrophage phagosomes, some bacterial pathogens such as Mycobacterium tuberculosis (Mtb) evade killing by preventing phagosome acidification and fusion of the phagosome with a lysosome. Mtb accumulates extracellular polyphosphate (polyP), and polyP inhibits macrophage phagosome acidification and bacterial killing. In Dictyostelium discoideum, polyP also inhibits bacterial killing, and we identified some proteins in D. discoideum that polyP requires to suppress the killing of ingested bacteria. Here, we find that pharmacological inhibition of human orthologues of the D. discoideum proteins, including P2Y1 receptors, mammalian target of rapamycin, and inositol hexakisphosphate kinase, enhances the killing of Mtb, Legion

SUBMITTER: Rijal R 

PROVIDER: S-EPMC12772234 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature