DataSheet_1_Studies of the Parasite-Midgut Interaction Reveal Plasmodium Proteins Important for Malaria Transmission to Mosquitoes.xlsx

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.

疟疾传播依赖于疟原虫与蚊子中肠的相互作用。学界推测，此类相互作用蛋白是阻断疟疾向蚊子传播的理想靶点。我们筛选得到76个携带信号肽编码区域、且在疟原虫有性阶段表达上调且丰度较高的基因。其中46个候选基因（占比60%）通过杆状病毒表达系统（baculovirus expression system）在昆虫细胞中完成了克隆与蛋白表达。其中6个蛋白被证实可与吸血蚊子的中肠裂解液发生相互作用，例如PF3D7_0303900、PF3D7_0406200（Pfs16）、PF3D7_1204400（Pfs37）、PF3D7_1214800、PF3D7_1239400以及PF3D7_1472800。既往研究显示，在伯氏疟原虫（Plasmodium berghei）中敲除Pfs37或Pfs16的同源基因，可减少蚊子体内的卵囊数量。本研究进一步发现，抗Pfs16多克隆抗体可显著抑制恶性疟原虫（Plasmodium falciparum）向冈比亚按蚊（Anopheles gambiae）的传播。对这些候选蛋白的研究，将加深我们对疟疾传播机制的理解，并助力发现阻断疟疾传播的全新靶点。