Evidence for the role of vacuolar soluble pyrophosphatase and inorganic polyphosphate in T rypanosoma cruzi persistence

Summary T rypanosoma cruzi infection leads to development of a chronic disease but the mechanisms that the parasite utilizes to establish a persistent infection despite activation of a potent immune response by the host are currently unknown. Unusual characteristics of T . cruzi are that it possesses cellular levels of pyrophosphate ( PP i ) at least 10 times higher than those of ATP and molar levels of inorganic polyphosphate ( polyP ) within acidocalcisomes. We characterized an inorganic soluble EF ‐hand containing pyrophosphatase from T . cruzi ( TcVSP ) that, depending on the pH and cofactors, can hydrolyse either pyrophosphate ( PP i ) or polyphosphate ( polyP ). The enzyme is localized to both acidocalcisomes and cytosol. Overexpression of TcVSP ( TcVSP‐OE ) resulted in a significant decrease in cytosolic PP i , and short and long‐chain polyP levels. Additionally, the TcVSP‐OE parasites showed a significant growth defect in fibroblasts, less responsiveness to hyperosmotic stress, and reduced persistence in tissues of mice, suggesting that PP i and polyP are essential for the parasite to resist the stressful conditions in the host and to maintain a persistent infection.