Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes.
Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes.
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DOI：
10.1016/j.cell.2008.04.051
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发表时间：
2008-07-11
期刊：
影响因子：
64.5
通讯作者：
Cowman AF
中科院分区：
文献类型：
--
作者：
Maier AG;Rug M;O'Neill MT;Brown M;Chakravorty S;Szestak T;Chesson J;Wu Y;Hughes K;Coppel RL;Newbold C;Beeson JG;Craig A;Crabb BS;Cowman AF
恶性疟原虫（Plasmodium falciparum）疟疾感染是人类最致命的寄生虫病，其毒力的主要部分是由受感染宿主红细胞的刚性和粘附性增加引起的。这些变化是由寄生虫蛋白质出口到红细胞使用新的运输机械组装在宿主细胞。为了理解这些独特的修饰，我们使用了一种大规模的基因敲除策略，结合功能筛选来鉴定输出到寄生虫感染的红细胞中并参与重塑这些细胞的蛋白质。鉴定了8个基因，其编码寄生虫粘附素PfEMP 1的输出和作为物理平台发挥锚粘附素功能的旋钮组装所需的蛋白质。此外，我们表明，多种蛋白质在感染红细胞刚性增加中发挥作用。这些蛋白质共同起病原体分泌系统的作用，类似于细菌，并且可以为每年导致数百万人死亡的疾病提供基于抗病力的疗法的靶标。
A major part of virulence for Plasmodium falciparum malaria infection, the most lethal parasitic disease of humans, results from increased rigidity and adhesiveness of infected host red cells. These changes are caused by parasite proteins exported to the erythrocyte using novel trafficking machinery assembled in the host cell. To understand these unique modifications, we used a large-scale gene knockout strategy combined with functional screens to identify proteins exported into parasite-infected erythrocytes and involved in remodeling these cells. Eight genes were identified encoding proteins required for export of the parasite adhesin PfEMP1 and assembly of knobs that function as physical platforms to anchor the adhesin. Additionally, we show that multiple proteins play a role in generating increased rigidity of infected erythrocytes. Collectively these proteins function as a pathogen secretion system, similar to bacteria and may provide targets for antivirulence based therapies to a disease responsible for millions of deaths annually.
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DOI：
10.4269/ajtmh.2007.77.22
发表时间：
2007-07-01
影响因子：
3.3
作者：
Beeson, James G.;Ndungu, Francis;Marsh, Kevin
通讯作者：
Marsh, Kevin
影响因子：
64.5
作者：
BARUCH, DI;PASLOSKE, BL;HOWARD, RJ
通讯作者：
HOWARD, RJ
影响因子：
1.5
作者：
Kun, JFJ;Hibbs, AR;Anders, RF
通讯作者：
Anders, RF
DOI：
10.1080/00365519850186049
发表时间：
1998-12-01
影响因子：
2.1
作者：
Hardeman, MR;Meinardi, MMHM;Vreeken, J
通讯作者：
Vreeken, J
影响因子：
1.5
作者：
Maier, Alexander G.;Braks, Joanna A. M.;Cowman, Alan F.
通讯作者：
Cowman, Alan F.