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Plasmodium falciparum evades immunity of anopheline mosquitoes by interacting with a Pfs47 midgut receptor.
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2020-01-22 , DOI: 10.1073/pnas.1917042117
Alvaro Molina-Cruz 1 , Gaspar E Canepa 2 , Thiago Luiz Alves E Silva 2 , Adeline E Williams 2 , Simardeep Nagyal 2 , Lampouguin Yenkoidiok-Douti 2 , Bianca M Nagata 2 , Eric Calvo 2 , John Andersen 2 , Martin J Boulanger 3 , Carolina Barillas-Mury 1
Affiliation  

The surface protein Pfs47 allows Plasmodium falciparum parasites to survive and be transmitted by making them "undetectable" to the mosquito immune system. P. falciparum parasites express Pfs47 haplotypes compatible with their sympatric vectors, while those with incompatible haplotypes are eliminated by the mosquito. We proposed that Pfs47 serves as a "key" that mediates immune evasion by interacting with a mosquito receptor "the lock," which differs in evolutionarily divergent anopheline mosquitoes. Recombinant Pfs47 (rPfs47) was used to identify the mosquito Pfs47 receptor protein (P47Rec) using far-Western analysis. rPfs47 bound to a single 31-kDa band and the identity of this protein was determined by mass spectrometry. The mosquito P47Rec has two natterin-like domains and binds to Pfs47 with high affinity (17 to 32 nM). P47Rec is a highly conserved protein with submicrovillar localization in midgut cells. It has structural homology to a cytoskeleton-interacting protein and accumulates at the site of ookinete invasion. Silencing P47Rec expression reduced P. falciparum infection, indicating that the interaction of Pfs47 with the receptor is critical for parasite survival. The binding specificity of P47Rec from distant anophelines (Anopheles gambiae, Anopheles dirus, and Anopheles albimanus) with Pfs47-Africa (GB4) and Pfs47-South America (7G8) haplotypes was evaluated, and it is in agreement with the previously documented compatibility between P. falciparum parasites expressing different Pfs47 haplotypes and these three anopheline species. Our findings give further support to the role of Pfs47 in the adaptation of P. falciparum to different vectors.

中文翻译:


恶性疟原虫通过与 Pfs47 中肠受体相互作用来逃避按蚊的免疫力。



表面蛋白 Pfs47 使恶性疟原虫寄生虫能够生存并通过使蚊子免疫系统“无法检测到”来传播。恶性疟原虫表达与其同域载体相容的 Pfs47 单倍型,而那些具有不相容单倍型的则被蚊子消除。我们提出Pfs47作为一把“钥匙”,通过与蚊子受体“锁”相互作用来介导免疫逃避,这在进化上趋异的按蚊中是不同的。重组 Pfs47 (rPfs47) 用于通过远西方分析鉴定蚊子 Pfs47 受体蛋白 (P47Rec)。 rPfs47 与单个 31 kDa 条带结合,并通过质谱法确定该蛋白质的身份。蚊子 P47Rec 具有两个 natterin 样结构域,并以高亲和力(17 至 32 nM)与 Pfs47 结合。 P47Rec 是一种高度保守的蛋白质,在中肠细胞中具有亚微绒毛定位。它与细胞骨架相互作用蛋白具有结构同源性,并在动动分子入侵位点积累。沉默 P47Rec 表达可减少恶性疟原虫感染,表明 Pfs47 与受体的相互作用对于寄生虫的生存至关重要。评估了来自远缘按蚊(冈比亚按蚊、大按蚊和白按蚊)的 P47Rec 与 Pfs47-非洲 (GB4) 和 Pfs47-南美洲 (7G8) 单倍型的结合特异性,这与之前记录的 P 之间的相容性一致。表达不同 Pfs47 单倍型的恶性疟原虫和这三种按蚊物种。我们的研究结果进一步支持了 Pfs47 在恶性疟原虫适应不同载体中的作用。
更新日期:2020-02-04
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