Plasmodium berghei PIMMS2 Promotes Ookinete Invasion of the Anopheles gambiae Mosquito Midgut.
Plasmodium berghei PIMMS2 Promotes Ookinete Invasion of the Anopheles gambiae Mosquito Midgut.
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DOI：
10.1128/iai.00139-17
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发表时间：
2017-08
影响因子：
3.1
通讯作者：
Vlachou D
中科院分区：
文献类型：
--
作者：
Ukegbu CV;Akinosoglou KA;Christophides GK;Vlachou D
疟原虫的中肠阶段是研究宿主-寄生虫相互作用和制定干预措施以阻断疾病传播的一个有吸引力的生物系统。蚊子感染伴随着动合子侵入和穿越蚊子中肠上皮的卵囊发育。在这里，我们报告的表征PIMMS 2（疟原虫入侵蚊子中肠筛选候选2），伯氏疟原虫蛋白与枯草杆菌蛋白酶样蛋白的结构相似性。PIMMS 2直系同源物存在于所有疟原虫的基因组中，并定位在枯草杆菌蛋白酶编码基因SUB1和SUB 3之间。伯氏疟原虫PIMMS 2在合子和动合子中特异性表达，并且定位于动合子表面。通过同源重组的基因破坏导致的PIMMS 2功能的丧失导致能动的动卵细胞的正常发育，所述动卵细胞表现出穿过蚊子中肠并转化为卵囊的能力严重受损。与突变的PIMMS 2等位基因的破坏位点的遗传互补揭示了对应于推定的枯草杆菌蛋白酶样催化三联体的氨基酸残基是重要的，但不是蛋白质功能所必需的。我们的数据表明，PIMMS 2是一种新的动合子特异性蛋白，促进寄生虫穿越蚊子中肠上皮和蚊子感染的建立。
Mosquito midgut stages of the malaria parasite present an attractive biological system to study host-parasite interactions and develop interventions to block disease transmission. Mosquito infection ensues upon oocyst development that follows ookinete invasion and traversal of the mosquito midgut epithelium. Here, we report the characterization of PIMMS2 (Plasmodium invasion of mosquito midgut screen candidate 2), a Plasmodium berghei protein with structural similarities to subtilisin-like proteins. PIMMS2 orthologs are present in the genomes of all plasmodia and are mapped between the subtilisin-encoding genes SUB1 and SUB3. P. berghei PIMMS2 is specifically expressed in zygotes and ookinetes and is localized on the ookinete surface. Loss of PIMMS2 function through gene disruption by homologous recombination leads to normal development of motile ookinetes that exhibit a severely impaired capacity to traverse the mosquito midgut and transform to oocysts. Genetic complementation of the disrupted locus with a mutated PIMMS2 allele reveals that amino acid residues corresponding to the putative subtilisin-like catalytic triad are important but not essential for protein function. Our data demonstrate that PIMMS2 is a novel ookinete-specific protein that promotes parasite traversal of the mosquito midgut epithelium and establishment of mosquito infection.