Polyphosphate in Host Cells and Pathogens

Polyphosphate Polyphosphate (polyP) is a linear polymer of a few to many hundreds of phosphate (Pi) residues linked by high-energy phosphoanhydride bonds. This ubiquitous polymer is found in bacteria, protists, and mammalian cells, and probably predates living cells. In bacteria, polyP accumulates in volutin or metachromatic granules, which are equivalent to acidocalcisomes. 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.

Acidocalcisomes were first described in trypanosomes and later found in Apicomplexan parasites, algae, slime molds, fungi, eggs of different origins, and human cells. These organelles were originally described as acidic compartments storing high concentrations of calcium, and later work found that they are highly enriched in polyP. As the description of acidocalcisomes progressed over the years, it was found that they are similar to the volutin or metachromic granules described in bacteria and are now considered to be the only organelles maintained over evolutionary time from bacteria to human cells.

The function of polyP has been studied mainly in prokaryotes: as a Pi store, an energy source to replace ATP, in cation sequestration and storage, in cell membrane formation and function, in gene transcription control, in regulation of enzyme activities, in response to stress and stationary phase, and in the structure of channels and pumps. PolyP is also important in the physiological adjustments of bacteria to growth, development, stress, and deprivation; its role in biofilm development, quorum sensing, and virulence, as well as in long-term survival and expression of virulence factors.

PolyP, which in bacteria is mainly of long-chain type (>300 and up to 1,000 Pi residues), has been reported to be important for virulence of different bacteria, such as Salmonella spp., Shigella flexneri, Vibrio cholerae, Neisseria meningitidis, Pseudomonas aeruginosa, and Mycobacterium tuberculosis, but the mechanism involved is not known. It has also been reported that conditions that decrease the levels of polyP in parasites such as T. brucei, T. gondii, or L. major reduce their pathogenicity. Whether this is due to osmotic fragility of the parasites as a result of changes in polyP levels that impact their ability to grow in vivo, making the immune response against them more successful, or to a role of polyP in modulating the immune response is not yet known.

PolyP has been found in bacterial to human cells and has been reported to be important for virulence of different bacteria and a number of parasites, including those that cause toxoplasmosis, African trypanosomiasis, and leishmaniasis. Even more exciting are the findings about the role of polyP in cancer metastasis, blood coagulation, inflammation, and innate immunity. For example, a significant finding is that enzymes involved in polyP metabolism could be excellent targets for drug design not only against bacteria and parasites but also for regulation of important physiological and pathological processes such as coagulation, inflammation, innate immunity, and thrombosis.

 

Polyphosphate and Its Diverse Functions in Host Cells and Pathogens. (2013) PLoS Pathog 9(5): e1003230. doi:10.1371/journal.ppat.1003230

 

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