title: Evidence for the role of vacuolar soluble pyrophosphatase and inorganic polyphosphate in Trypanosoma cruzi persistence.
abstract: Trypanosoma 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 (PPi ) 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 (PPi ) or polyphosphate (polyP). The enzyme is localized to both acidocalcisomes and cytosol. Overexpression of TcVSP (TcVSP-OE) resulted in a significant decrease in cytosolic PPi , 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 PPi and polyP are essential for the parasite to resist the stressful conditions in the host and to maintain a persistent infection.
authors.affiliation: Center for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, GA, 30602, USA.
authors.forename: Melina
authors.initials: M
authors.lastname: Galizzi
authors.forename: Juan M
authors.initials: JM
authors.lastname: Bustamante
authors.forename: Jianmin
authors.initials: J
authors.lastname: Fang
authors.forename: Kildare
authors.initials: K
authors.lastname: Miranda
authors.forename: Lia C
authors.initials: LC
authors.lastname: Soares Medeiros
authors.forename: Rick L
authors.initials: RL
authors.lastname: Tarleton
authors.forename: Roberto
authors.initials: R
authors.lastname: Docampo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D014355:Chagas Disease / Q000469:parasitology*; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D011756:Diphosphates / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011122:Polyphosphates / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D014617:Vacuoles / Q000201:enzymology; D014709:Vero Cells; D037521:Virulence Factors / Q000235:genetics
chemical_list: D011756:Diphosphates; D011122:Polyphosphates; D015800:Protozoan Proteins; D037521:Virulence Factors; D011755:Pyrophosphatases
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