Studies of the Parasite-Midgut Interaction Reveal Plasmodium Proteins Important for Malaria Transmission to Mosquitoes.

Studies of the Parasite-Midgut Interaction Reveal Plasmodium Proteins Important for Malaria Transmission to Mosquitoes.
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DOI:
10.3389/fcimb.2021.654216
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发表时间:
2021
影响因子:
5.7
通讯作者:
Li J
Li J
中科院分区:
医学2区
文献类型:
--
作者:
Niu G;Cui Y;Wang X;Keleta Y;Li J

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疟疾传播依赖于寄生虫-蚊子中肠相互作用。相互作用蛋白被假设为阻断疟疾向蚊子传播的理想靶点。我们选择了76个包含信号肽编码区域的基因,这些基因在性阶段被上调并高度丰富。其中46个候选基因(60%)被克隆并利用杆状病毒表达系统在昆虫细胞中表达。其中,PF3D7_0303900、PF3D7_0406200 (Pfs16)、PF3D7_1204400 (Pfs37)、PF3D7_1214800、PF3D7_1239400、PF3D7_1472800 6个菌株与血供蚊子中肠裂解液发生相互作用。先前的研究表明,在这些相互作用蛋白中,敲除伯氏疟原虫中Pfs37或Pfs16的同源物可以减少蚊子的卵囊。本研究进一步发现,抗pfs16多克隆抗体能显著抑制恶性疟原虫向冈比亚按蚊的传播。研究这些候选蛋白将提高我们对疟疾传播的认识,并发现阻断疟疾传播的新靶点。
Malaria transmission relies on parasite-mosquito midgut interaction. The interactive proteins are hypothesized to be ideal targets to block malaria transmission to mosquitoes. We chose 76 genes that contain signal peptide-coding regions and are upregulated and highly abundant at sexual stages. Forty-six of these candidate genes (60%) were cloned and expressed using the baculovirus expression system in insect cells. Six of them, e.g., PF3D7_0303900, PF3D7_0406200 (Pfs16), PF3D7_1204400 (Pfs37), PF3D7_1214800, PF3D7_1239400, and PF3D7_1472800 were discovered to interact with blood-fed mosquito midgut lysate. Previous works showed that among these interactive proteins, knockout the orthologs of Pfs37 or Pfs16 in P. berghei reduced oocysts in mosquitoes. Here we further found that anti-Pfs16 polyclonal antibody significantly inhibited P. falciparum transmission to Anopheles gambiae. Investigating these candidate proteins will improve our understanding of malaria transmission and discover new targets to break malaria transmission.
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