Leishmania donovani singly deficient in HGPRT, APRT or XPRT are viable in vitro and within mammalian macrophages
Leishmania donovani singly deficient in HGPRT, APRT or XPRT are viable in vitro and within mammalian macrophages
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DOI：
10.1016/j.molbiopara.2006.02.015
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发表时间：
2006-07-01
影响因子：
1.5
通讯作者：
Ullman, Buddy
中科院分区：
文献类型：
--
作者：
Boitz, Jan M.;Ullman, Buddy
利什曼原虫表达三种磷酸核糖基转移酶，次黄嘌呤-鸟嘌呤磷酸核糖基转移酶（HGPRT），腺嘌呤磷酸核糖基转移酶（APRT）和黄嘌呤磷酸核糖基转移酶（XPRT），使该属从其宿主获得嘌呤营养。为了测试这些酶中的任何一种是否对于哺乳动物巨噬细胞内的活力、转化成无鞭毛体以及感染性和增殖是必需的，通过在杜氏利什曼原虫的毒性背景内的靶向基因置换来产生Δ hgprt、Δ aprt和Δ xprt无效突变体。三个基因敲除菌株中的每一个作为前鞭毛体和纯无鞭毛体都是可行的，并且能够在骨髓源性小鼠巨噬细胞中维持感染。这些数据支持的假设，没有三个磷酸核糖转移酶是必不可少的嘌呤救助或生存能力本身，嘌呤救助发生通过多种合成代谢途径在两个寄生虫的生命周期阶段。此外，这些研究揭示了腺嘌呤氨基水解酶在L。donovani纯无鞭毛体，以前认为仅限于前鞭毛体的活动。(c)2006 Elsevier B. V.保留所有权利。
Leishmania species express three phosphoribosyltransferase enzymes, hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenine phosphoribosyltransferase (APRT), and xanthine phosphoribosyltransferase (XPRT), which enable this genus to acquire purine nutrients from their hosts. To test whether any of these enzymes is essential for viability, transformation into amastigotes, and infectivity and proliferation within mammalian macrophages, Delta hgprt, Delta aprt, and Delta xprt null mutants were created by targeted gene replacement within a virulent background of Leishmania donovani. Each of the three knockout strains was viable as promastigotes and axenic amastigotes and capable of maintaining an infection in bone marrow-derived murine macrophages. These data support the hypothesis that none of the three phosphoribosyltransferases is essential for purine salvage or viability by itself and that purine salvage occurs through multiple anabolic routes in both parasite life cycle stages. In addition these studies revealed the presence of an adenine aminohydrolase enzyme in L. donovani axenic amastigotes, an activity previously thought to be restricted to promastigotes. (c) 2006 Elsevier B.V. All rights reserved.