Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasite Plasmodium knowlesi
Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasite Plasmodium knowlesi
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DOI：
10.1073/pnas.1522469113
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发表时间：
2016-06-28
影响因子：
11.1
通讯作者：
Holder, Anthony A.
中科院分区：
文献类型：
--
作者：
Moon, Robert W.;Sharaf, Hazem;Holder, Anthony A.
马来西亚疟疾的主要病因现在是诺氏疟原虫，这是一种在东南亚各地发现的食蟹猕猴的人畜共患寄生虫。对适应食蟹蟹和人红细胞体外生长的寄生虫进行基因组比较分析，发现在食蟹蟹红细胞中生长的寄生虫中有一个基因组缺失，其中包括编码正常细胞结合蛋白Xa （NBPXa）的基因，而在人红细胞中没有。在适应在人红细胞中生长的寄生虫（保留在食蟹红细胞中生长的能力）中，实验删除NBPXa基因，将它们限制在食蟹红细胞中，这表明该基因是寄生虫在人红细胞中增殖和生长的选择性必需基因。不含nbpxa的寄生虫可以与人红细胞结合，但对这些细胞的侵袭受到严重损害。因此，NBPXa被确定为诺氏疟原虫人感染的关键媒介，可能是针对这种新出现的病原体开发疫苗的靶点。
The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.