Bacterial polyphosphates interfere with the innate host defense to infection

Julian Roewe, Georgios Stavrides, Marcel Strueve, Arjun Sharma, Federico Marini, Amrit Mann, Stephanie A. Smith, Ziya Kaya, Birgit Strobl, Mathias Mueller, Christoph Reinhardt, James H. Morrissey and Markus Bosmann ()
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Julian Roewe: University Medical Center Mainz
Georgios Stavrides: University Medical Center Mainz
Marcel Strueve: University Medical Center Mainz
Arjun Sharma: University Medical Center Mainz
Federico Marini: University Medical Center Mainz
Amrit Mann: University Medical Center Mainz
Stephanie A. Smith: University of Michigan Medical School
Ziya Kaya: University of Heidelberg
Birgit Strobl: University of Veterinary Medicine Vienna
Mathias Mueller: University of Veterinary Medicine Vienna
Christoph Reinhardt: University Medical Center Mainz
James H. Morrissey: University of Michigan Medical School
Markus Bosmann: University Medical Center Mainz

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Polyphosphates are linear polymers and ubiquitous metabolites. Bacterial polyphosphates are long chains of hundreds of phosphate units. Here, we report that mouse survival of peritoneal Escherichia coli sepsis is compromised by long-chain polyphosphates, and improves with bacterial polyphosphatekinase deficiency or neutralization using recombinant exopolyphosphatase. Polyphosphate activities are chain-length dependent, impair pathogen clearance, antagonize phagocyte recruitment, diminish phagocytosis and decrease production of iNOS and cytokines. Macrophages bind and internalize polyphosphates, in which their effects are independent of P2Y1 and RAGE receptors. The M1 polarization driven by E. coli derived LPS is misdirected by polyphosphates in favor of an M2 resembling phenotype. Long-chain polyphosphates modulate the expression of more than 1800 LPS/TLR4-regulated genes in macrophages. This interference includes suppression of hundreds of type I interferon-regulated genes due to lower interferon production and responsiveness, blunted STAT1 phosphorylation and reduced MHCII expression. In conclusion, prokaryotic polyphosphates disturb multiple macrophage functions for evading host immunity.

Date: 2020
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DOI: 10.1038/s41467-020-17639-x

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