Targeted disruption of the plasmodium berghei CTRP gene reveals its essential role in malaria infection of the vector mosquito.
Targeted disruption of the plasmodium berghei CTRP gene reveals its essential role in malaria infection of the vector mosquito.
复制标题
伯氏疟原虫 CTRP 基因的靶向破坏揭示了其在媒介蚊子疟疾感染中的重要作用。
DOI：
10.1084/jem.190.11.1711
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发表时间：
1999-12-06
影响因子：
15.3
通讯作者：
Chinzei, Y
中科院分区：
文献类型：
--
作者：
Yuda, M;Sakaida, H;Chinzei, Y
啮齿类疟疾寄生虫伯氏疟原虫（Plasmodium berghei，PbCTRP）的CTRP（环子孢子蛋白和血小板反应蛋白相关粘附蛋白[TRAP]相关蛋白）与在宿主侵入阶段1中特异性表达的其它顶复体蛋白一起构成蛋白质家族。PbCTRP在蚊子侵入或动合子阶段产生，并且是在蚊子中肠上皮的动合子粘附和侵入中起作用的蛋白质候选物。为了证明PbCTRP参与载体的感染，我们用该基因进行了靶向破坏实验。PbCTRP破坏表现出正常的出丝率和发展成动合子。然而，没有卵囊形成后，观察到这些寄生虫摄入中肠，这表明他们的入侵能力完全丧失。另一方面，当与野生型寄生虫一起摄入时，干扰物能够感染蚊子，这表明野生型寄生虫的PbCTRP基因在蚊子中肠腔中异源交配时挽救了干扰物的感染性。我们的研究结果表明，PbCTRP在疟疾感染的蚊子中肠中起着至关重要的作用，并表明疟疾寄生虫使用类似的分子机制来入侵昆虫载体和哺乳动物宿主中的细胞。
CTRP (circumsporozoite protein and thrombospondin-related adhesive protein [TRAP]-related protein) of the rodent malaria parasite Plasmodium berghei (PbCTRP) makes up a protein family together with other apicomplexan proteins that are specifically expressed in the host-invasive stage 1. PbCTRP is produced in the mosquito-invasive, or ookinete, stage and is a protein candidate for a role in ookinete adhesion and invasion of the mosquito midgut epithelium. To demonstrate involvement of PbCTRP in the infection of the vector, we performed targeting disruption experiments with this gene. PbCTRP disruptants showed normal exflagellation rates and development into ookinetes. However, no oocyst formation was observed in the midgut after ingestion of these parasites, suggesting complete loss of their invasion ability. On the other hand, when ingested together with wild-type parasites, disruptants were able to infect mosquitoes, indicating that the PbCTRP gene of the wild-type parasite rescued infectivity of disruptants when they heterologously mated in the mosquito midgut lumen. Our results show that PbCTRP plays a crucial role in malaria infection of the mosquito midgut and suggest that similar molecular mechanisms are used by malaria parasites to invade cells in the insect vector and the mammalian host.