Polyphosphate is an extracellular signal that can facilitate bacterial survival in eukaryotic cells
Ramesh Rijal, Louis A. Cadena, Morgan Smith, Joseph F. Carr, Richard H. Gomer
Abstract
Significance Macrophages use phagocytosis to engulf bacteria such as E. coli and kill them. Pathogenic bacteria such as Mycobacterium tuberculosis are similarly ingested, but not killed, by macrophages. We find that M. smegmatis and M. tuberculosis bacteria accumulate high levels of extracellular polyphosphate compared to E. coli and survive better after phagocytosis in Dictyostelium discoideum or macrophages. The addition of polyphosphate causes some D. discoideum or macrophages to keep ingested nonpathogenic E. coli bacteria alive. Conversely, exopolyphosphatase, an enzyme that degrades polyphosphate, causes D. discoideum and macrophages to kill more of the ingested bacteria. Polyphosphate inhibits phagosome acidification and lysosome activity in D. discoideum and macrophages, suggesting that extracellular or intraphagosomal polyphosphate activates a pathway to potentiate viability of ingested bacteria.