Host metabolism regulates growth and differentiation of Toxoplasma gondii.
Host metabolism regulates growth and differentiation of Toxoplasma gondii.
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DOI：
10.1016/j.ijpara.2012.07.011
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发表时间：
2012-09
影响因子：
4
通讯作者：
Sha WC
中科院分区：
文献类型：
--
作者：
Weilhammer DR;Iavarone AT;Villegas EN;Brooks GA;Sinai AP;Sha WC
弓形虫发病机制中的一个关键步骤是从急性感染期间经历的快速复制的速殖子形式转变为缓慢复制的缓殖子形式，从而在慢性感染期间形成长寿命的组织包囊。缓殖子包囊发育在体内表现出明显的组织向性，但影响这种向性的宿主细胞环境条件仍不清楚。使用缓殖子转化的体外测定，我们发现细胞类型在促进速殖子分化为缓殖子的能力方面存在显着差异。对转化耐药或允许的细胞类型的表征表明，耐药细胞系释放低分子量代谢物，这些代谢物可以在代谢应激条件下支持速殖子的生长，从而抑制允许细胞中缓殖子的形成。生化分析表明，糖酵解代谢物乳酸是耐药细胞上清液的抑制成分。此外，通过添加葡萄糖或通过宿主激酶 Akt 的过度表达来上调许可细胞中的糖酵解，足以将细胞从许可表型转化为抗性表型。这些结果表明，宿主细胞的代谢状态可能在决定寄生虫从速殖子形式转变为缓殖子形式的倾向中发挥作用。
A critical step in the pathogenesis of Toxoplasma gondii is conversion from the fast-replicating tachyzoite form experienced during acute infection to the slow-replicating bradyzoite form that establishes long-lived tissue cysts during chronic infection. Bradyzoite cyst development exhibits a clear tissue tropism in vivo, yet conditions of the host cell environment that influence this tropism remain unclear. Using an in vitro assay of bradyzoite conversion, we have found that cell types differ dramatically in the ability to facilitate differentiation of tachyzoites into bradyzoites. Characterization of cell types that were either resistant or permissive for conversion revealed that resistant cell lines release low molecular weight metabolites that could support tachyzoite growth under metabolic stress conditions and thereby inhibit bradyzoite formation in permissive cells. Biochemical analysis revealed that the glycolytic metabolite lactate is an inhibitory component of supernatants from resistant cells. Furthermore, upregulation of glycolysis in permissive cells through the addition of glucose or by overexpression of the host kinase, Akt, was sufficient to convert cells from a permissive to a resistant phenotype. These results suggest that the metabolic state of the host cell may play a role in determining the predilection of the parasite to switch from the tachyzoite to bradyzoite form.
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影响因子：
3.1
作者：
BOHNE, W;HEESEMANN, J;GROSS, U
通讯作者：
GROSS, U
DOI：
10.1016/0169-4758(96)80642-9
发表时间：
1996-01-01
期刊：
PARASITOLOGY TODAY
影响因子：
--
作者：
Gross, U;Bohne, W;Dubremetz, JF
通讯作者：
Dubremetz, JF
影响因子：
2.1
作者：
Lüder, CGK;Giraldo-Velásquez, M;Gross, U
通讯作者：
Gross, U
影响因子：
4.8
作者：
Blader, IJ;Manger, ID;Boothroyd, JC
通讯作者：
Boothroyd, JC
影响因子：
3.1
作者：
Manger, ID;Hehl, A;Boothroyd, JC
通讯作者：
Boothroyd, JC