Polyphosphate and Its Diverse Functions in Host Cells and Pathogens

Polyphosphate (polyP) is a linear polymer of a few to many hundreds of phosphate (Pi) 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, Mg, Zn, Fe, 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 Pi) and long-chain (from 300 to ,1000 Pi) 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.