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穿孔素样蛋白PPLP4对恶性疟原虫感染蚊子中肠至关重要。

Perforin-like protein PPLP4 is crucial for mosquito midgut infection by Plasmodium falciparum.

作者信息

Wirth Christine C, Bennink Sandra, Scheuermayer Matthias, Fischer Rainer, Pradel Gabriele

机构信息

Cellular and Applied Infection Biology Section, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany.

Research Center for Infectious Diseases, University of Würzburg, Josef-Schneider-Str. 2/D15, 97080 Würzburg, Germany.

出版信息

Mol Biochem Parasitol. 2015 Jun;201(2):90-9. doi: 10.1016/j.molbiopara.2015.06.005. Epub 2015 Jul 9.

DOI:10.1016/j.molbiopara.2015.06.005
PMID:26166358
Abstract

The genomes of Plasmodium parasites encode for five perforin-like proteins, PPLP1-5, and four of them have previously been demonstrated to be involved in disruption of host cell barriers. We now show that the fifth perforin, PPLP4, is crucial for infection of the mosquito vector by Plasmodium falciparum parasites. PPLP4 is expressed in the blood and mosquito midgut stages in granular structures. In gametocytes, PPLP4 expression is specific to the female gender, while ookinetes show a PPLP4 localization at the apical pole. Gene disruption of pplp4 results in no phenotypical change during blood stage replication, gametocyte development or gametogenesis, while mosquitoes fed with PPLP4-deficient gametocytes display a severe reduction in oocyst numbers, and an accumulation of ookinetes in the mosquito midguts was observed. In conclusion, we propose an essential role for PPLP4 in infection of the mosquito midgut, presumably by mediating ookinete traversal through the midgut epithelium.

摘要

疟原虫的基因组编码五种穿孔素样蛋白,即PPLP1 - 5,其中四种先前已被证明参与破坏宿主细胞屏障。我们现在表明,第五种穿孔素PPLP4对于恶性疟原虫感染蚊媒至关重要。PPLP4在血液和蚊中肠阶段以颗粒结构表达。在配子体中,PPLP4的表达具有雌性特异性,而动合子则在顶端极显示PPLP4定位。pplp4基因破坏在血液阶段复制、配子体发育或配子发生过程中未导致表型变化,而喂食缺乏PPLP4的配子体的蚊子显示卵囊数量严重减少,并且在蚊中肠中观察到动合子的积累。总之,我们提出PPLP4在感染蚊中肠中起重要作用,可能是通过介导动合子穿过中肠上皮。

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