Evidence for the role of vacuolar soluble pyrophosphatase and inorganic polyphosphate in Trypanosoma cruzi persistence.
Evidence for the role of vacuolar soluble pyrophosphatase and inorganic polyphosphate in Trypanosoma cruzi persistence.
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DOI：
10.1111/mmi.12392
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发表时间：
2013-11
影响因子：
3.6
通讯作者：
Docampo R
中科院分区：
文献类型：
--
作者：
Galizzi M;Bustamante JM;Fang J;Miranda K;Soares Medeiros LC;Tarleton RL;Docampo R
克氏锥虫感染可导致慢性疾病的发展，但尽管宿主激活了强有力的免疫反应，但寄生虫建立持续感染的机制目前尚不清楚。t . cruzi的不同寻常的特点是它具有细胞水平的焦磷酸(PPi)至少十倍的ATP和摩尔水平的无机多磷酸盐在acidocalcisomes(息肉)。我们鉴定了一种含有克氏T. crozi焦磷酸酶（TcVSP）的无机可溶性EF-hand，根据pH和辅助因子的不同，它可以水解焦磷酸盐（PPi）或聚磷酸盐（polyP）。该酶定位于酸溶酶体和细胞质。过表达TcVSP （TcVSP- oe）导致胞浆PPi、短链和长链息肉p水平显著降低。此外，TcVSP-OE寄生虫在成纤维细胞中表现出明显的生长缺陷，对高渗应激的反应性较低，在小鼠组织中的持久性降低，这表明PPi和息肉p对于寄生虫抵抗宿主的应激条件和维持持续感染至关重要。
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 ten 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 hydrolyze 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.
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影响因子：
2.2
作者：
Kollien, AH;Grospietsch, T;Schaub, GA
通讯作者：
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影响因子：
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作者：
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作者：
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DOI：
10.1073/pnas.1217816110
发表时间：
2013-01-22
影响因子：
11.1
作者：
Luoto, Heidi H.;Baykov, Alexander A.;Malinen, Anssi M.
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DOI：
10.1080/07315724.2007.10719667
发表时间：
2007-10-01
影响因子：
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作者：
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Lang, Florian