Journal
MBIO
Volume -, Issue -, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/mbio.01939-23
Keywords
polyphosphate; Dictyostelium; phagocytosis; bacterial survival
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Research has discovered that polyphosphate (polyP) inhibits the killing ability of macrophages towards ingested bacteria by utilizing the G protein-coupled receptor (GPCR) and other components in the signal transduction pathway. Additionally, high concentrations of polyP also inhibit cell division. These findings suggest that pharmacologically blocking the polyP inhibition of bacterial killing pathway may enhance the killing of pathogenic bacteria by macrophages.
Human macrophages and the eukaryotic microbe Dictyostelium discoideum ingest bacteria by phagocytosis, and then kill the ingested bacteria. Some pathogenic bacteria secrete linear chains of phosphate residues (polyphosphate; polyP), and the polyP prevents some of the phagocytes from killing the ingested bacteria. In D. discoideum, the effect of polyP requires the G protein-coupled receptor (GPCR) GrlD, suggesting that polyP uses a signal transduction pathway to inhibit killing of ingested bacteria. Here we show that in addition to GrlD, the D. discoideum polyP signaling pathway requires the GPCR interacting arrestin-like protein AdcB, inositol hexakisphosphate kinase A (I6kA), the Rho GTPase RacE, and the target of rapamycin (TOR) component Lst8. D. discoideum also secretes polyP, and at high concentrations polyP inhibits D. discoideum cytokinesis. The polyP inhibition of bacterial killing pathway has some components that overlap and some components that are distinct from the polyP inhibition of cytokinesis pathway. These data suggest the intriguing possibility that if there is a similar polyP inhibition of bacterial killing pathway in macrophages, pharmacologically blocking this pathway could potentiate macrophage killing of pathogenic bacteria.
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