Polyphosphate is an Extracellular Signal That Can Facilitate Bacterial Survival in Eukaryotic Cells

Polyphosphate is a linear chain of phosphate residues and is present in organisms ranging from bacteria to humans. Pathogens such as accumulate polyphosphate, and reduced expression of the polyphosphate kinase that synthesizes polyphosphate decreases their survival. How polyphosphate potentiates pathogenicity is poorly understood. K-12 do not accumulate detectable levels of extracellular polyphosphate and have poor survival after phagocytosis by or human macrophages. In contrast, and accumulate detectable levels of extracellular polyphosphate, and have relatively better survival after phagocytosis by or macrophages. Adding extracellular polyphosphate increased survival after phagocytosis by and macrophages. Reducing expression of polyphosphate kinase 1 in reduced extracellular polyphosphate and reduced survival in and macrophages, and this was reversed by the addition of extracellular polyphosphate. Conversely, treatment of and macrophages with recombinant yeast exopolyphosphatase reduced the survival of phagocytosed or cells lacking the putative polyphosphate receptor GrlD had reduced sensitivity to polyphosphate and, compared to wild-type cells, showed increased killing of phagocytosed and Polyphosphate inhibited phagosome acidification and lysosome activity in and macrophages and reduced early endosomal markers in macrophages. Together, these results suggest that bacterial polyphosphate potentiates pathogenicity by acting as an extracellular signal that inhibits phagosome maturation.