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红细胞结合蛋白的顺序作用使得疟疾寄生虫的入侵能够逐步承诺

Melissa N Hart^1,2, Franziska Mohring¹, Sophia M DonVito¹

¹Department of Infection Biology, Faculty of Infectious and Tropical Disease, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.

Nature communications

|August 1, 2023

概括

红细胞 (RBC) 的Plasmodium knowlesi入侵依赖于特定的Duffy结合性蛋白质 (DBPs) 和网细胞结合性蛋白质 (RBLs). 这些蛋白质的不同作用揭示了可能被抗体准的阶段性入侵机制.

科学领域:

疟疾学疟疾学
寄生虫学的寄生虫学
分子生物学分子生物学

背景情况:

红细胞 (RBC) 受到Plasmodium merozoites的入侵对于疟疾寄生虫的生存至关重要.
达菲结合样蛋白 (DBPs) 和网细胞结合样蛋白 (RBLs) 是红细胞入侵等菌物种的关键媒介.
动物性疟疾寄生虫Plasmodium knowlesi与Plasmodium falciparum相比,具有精简的入侵蛋白质谱.

研究的目的:

阐明DBP和RBL介导的Plasmodium知识中的关键入侵事件的精确角色和顺序顺序.
调查DBPα和NBPXa在P. knowlesi.的入侵人类红细胞中的独特功能.
探索疟疾侵袭抑制剂的潜在协同治疗点.

主要方法:

使用代的CRISPR-Cas9基因组编辑在Plasmodium知识库中.
利用P. knowlesi独特的生物特征进行入侵研究.
确定了关键宿主细胞入侵里程碑的时间序列.

主要成果:

证明了DBP和RBL蛋白家族在P. knowlesi入侵中具有不同的功能作用.
确立了DBPα和NBPXa对人类红细胞P. knowlesi.入侵的关键性.
鉴定了一种阶段性承诺机制,该机制是 merozoite 侵袭的基础.

结论:

P. knowlesi DBPs和RBLs的不同角色支持分阶段入侵承诺的模式.
这种分阶段的机制为抗体的协同抑制提供了一个可行的目标.
了解这些不同角色对于开发新的抗疟疾战略至关重要.

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