Polyphosphate is an extracellular signal that can facilitate bacterial survival in eukaryotic cells. | Academic Article individual record
abstract

Polyphosphate is a linear chain of phosphate residues and is present in organisms ranging from bacteria to humans. Pathogens such as Mycobacterium tuberculosis accumulate polyphosphate, and reduced expression of the polyphosphate kinase that synthesizes polyphosphate decreases their survival. How polyphosphate potentiates pathogenicity is poorly understood. Escherichia coli K-12 do not accumulate detectable levels of extracellular polyphosphate and have poor survival after phagocytosis by Dictyostelium discoideum or human macrophages. In contrast, Mycobacterium smegmatis and Mycobacterium tuberculosis accumulate detectable levels of extracellular polyphosphate, and have relatively better survival after phagocytosis by D. discoideum or macrophages. Adding extracellular polyphosphate increased E. coli survival after phagocytosis by D. discoideum and macrophages. Reducing expression of polyphosphate kinase 1 in M. smegmatis reduced extracellular polyphosphate and reduced survival in D. discoideum and macrophages, and this was reversed by the addition of extracellular polyphosphate. Conversely, treatment of D. discoideum and macrophages with recombinant yeast exopolyphosphatase reduced the survival of phagocytosed M. smegmatis or M. tuberculosis D. discoideum cells lacking the putative polyphosphate receptor GrlD had reduced sensitivity to polyphosphate and, compared to wild-type cells, showed increased killing of phagocytosed E. coli and M. smegmatis Polyphosphate inhibited phagosome acidification and lysosome activity in D. discoideum 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.

publication outlet

Proc Natl Acad Sci U S A

author list (cited authors)
Rijal, R., Cadena, L. A., Smith, M. R., Carr, J. F., & Gomer, R. H.
publication date
2020
keywords
  • Primary Cell Culture
  • Bacteria
  • Exopolyphosphatase
  • Saccharomyces Cerevisiae Proteins
  • Humans
  • Recombinant Proteins
  • Polyphosphate Kinase
  • Lysosomes
  • Phagocytosis
  • Cells, Cultured
  • Acid Anhydride Hydrolases
  • Burkholderia
  • Hydrogen-Ion Concentration
  • Macrophages
  • Polyphosphate
  • Mycobacterium Tuberculosis
  • Phagosomes
  • Polyphosphates
  • Healthy Volunteers
  • Dictyostelium
altmetric score

0.75

citation count

7

PubMed ID
33268492
identifier
546602SE
Digital Object Identifier (DOI)
start page
31923
end page
31934
volume
117
issue
50