Bacterial-Type Long-Chain Polyphosphates Bind Human Proteins in the Phosphatidylinositol Signaling Pathway

Introduction

Inorganic polyphosphates are linear polymers of monophosphate residues (P_i) that exist as short chains (P_i30–120) in platelet δ-granules and as long chains in bacteria.[1] A higher chain length increases the activity of these anionic polymers to accelerate factor XIIa-mediated factor XI activation, thrombin generation, block tissue factor pathway inhibitor activity, and strengthen fibrin clots by enhancing their mechanical stability and resistance to fibrinolysis.[2] [3] In bacteria, polyphosphates are associated with energy and phosphate storage, stress resistance, chelation of metal ions, and escaping host immunity.[4] During severe infections, long-chain polyphosphates from bacteria contribute to coagulopathy, neutrophil extracellular trap formation, and vascular-endothelial dysfunction.[3] [5] [6] However, the mechanisms that convey the pleiotropic activities of polyphosphates in living cells remain understudied.

^* These authors contributed equally.

Publication History

Received: 10 December 2021

Accepted: 17 May 2022

Article published online:
30 July 2022

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