Polyphosphate and Its Diverse Functions in Host Cells and Pathogens

Polyphosphate (polyP) is a linear polymer of a few to many hundreds of phosphate (P i ) residues linked by high-energy phosphoanhydride bonds (Figure 1A).This ubiquitous polymer is found in bacteria, protists, and mammalian cells, and it was likely present prebiotically [1].In bacteria, polyP accumulates in volutin or metachromatic granules, which are equivalent to acidocalcisomes [2].In eukaryotic cells, polyP is present in different compartments, including the cytosol, nucleus, lysosomes, and mitochondria, but is preferentially accumulated in acidic vacuoles such as the yeast vacuole and acidocalcisomes [1,3].In these organelles, polyP, which is negatively charged, is in close association of inorganic (Ca 2+ , Mg 2+ , Zn 2+ , Fe 2+ , Na + , K + ) and organic (basic amino acids, polyamines) cations.PolyP also combines with calcium and polyhydroxybutyrate forming channels in bacterial membranes, which make them competent for DNA entry; in mitochondria, as part of the mitochondrial permeability transition pore; and in the plasma membrane, as part of the potassium channel and the calcium pump (reviewed in [1,4]).PolyP is arbitrarily divided into two forms: short-chain (from 3 to ,300 P i ) and long-chain (from 300 to ,1000 P i ) polyP, based on the method used for its extraction.For the detection of polyP, several methods have been described and a few examples are shown in Figure 1B-F.