Characterization of a Sulfhydryl Oxidase From Plasmodium berghei as a Target for Blocking Parasite Transmission
Characterization of a Sulfhydryl Oxidase From Plasmodium berghei as a Target for Blocking Parasite Transmission
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伯氏疟原虫巯基氧化酶作为阻断寄生虫传播靶标的表征
DOI：
10.3389/fcimb.2020.00311
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发表时间：
2020-06
影响因子：
5.7
通讯作者：
Yaming Cao
中科院分区：
文献类型：
--
作者：
Wenqi Zheng;Fei Liu;Feng Du;Fan Yang;Xu Kou;Yiwen He;Hui Feng;Qi Fan;Enjie Luo;Hui Min;Jun Miao;Liwang Cui;Yaming Cao
Quiescin巯基氧化酶（QSOX）存在于多种真核生物中，催化二硫键插入未折叠的还原蛋白质中。在这里，我们表征了来自啮齿动物疟原虫伯氏疟原虫（PbQSOX）的QSOX蛋白，该蛋白在所有已测序的疟原虫物种中都是保守的。PbQSOX蛋白在无性红细胞阶段不表达，但在动合子中表达最丰富。间接免疫荧光检测显示PbQSOX不仅定位于配子母细胞、配子和动合子的细胞质中，而且在配子和动合子的表面也有表达。蛋白质印迹法鉴定动合子培养基中细胞外存在PbQSOX，提示分泌。Pbqsox缺失（Δpbqsox）不影响红细胞内的无性发育，但减少雄配子体的出丝和动合子的形成与成熟。Pbqsox缺失还导致动合子表面蛋白的还原巯基显著增加，这表明它可能在维持动合子发育所需的表面蛋白二硫键的完整性方面发挥作用。以Δ pbqsox感染小鼠为食的蚊子与以野生型寄生虫感染小鼠为食的蚊子相比，其动合子和卵囊数量显着减少。此外，针对重组PbQSOX的多克隆小鼠抗血清和单克隆抗体在体外和蚊子喂养试验中表现出显著的传播阻断活性，表明QSOX是阻断寄生虫传播的潜在靶标。
Quiescin sulfhydryl oxidase (QSOX), present in a wide variety of eukaryotic species, catalyzes the insertion of disulfide bonds into unfolded, reduced proteins. Here we characterized the QSOX protein from the rodent malaria parasite Plasmodium berghei (PbQSOX), which is conserved in all sequenced malaria parasite species. The PbQSOX protein was not expressed in asexual erythrocytic stages, but was most abundantly expressed in ookinetes. Indirect immunofluorescence assays revealed PbQSOX was not only localized in cytoplasm of gametocytes, gametes and ookinetes, but also expressed on the surface of gametes and ookinetes. Western blot identified extracellular presence of PbQSOX in the culture medium of ookinetes suggestive of secretion. Pbqsox deletion (Δpbqsox) did not affect asexual intraerythrocytic development, but reduced exflagellation of male gametocytes as well as formation and maturation of ookinetes. Pbqsox deletion also led to a significant increase in the reduced thiol groups of ookinete surface proteins, suggesting that it may play a role in maintaining the integrity of disulfide bonds of surface proteins, which might be needed for ookinete development. Mosquitoes that fed on Δpbqsox-infected mice showed a significant reduction in ookinete and oocyst numbers compared to those fed on wild-type parasite-infected mice. Further, both polyclonal mouse antisera and a monoclonal antibody against the recombinant PbQSOX exhibited substantial transmission-blocking activities in in vitro and mosquito feeding assays, suggesting QSOX is a potential target for blocking parasite transmission.
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DOI：
10.1016/s0140-6736(15)00417-1
发表时间：
2016-04-23
期刊：
Lancet (London, England)
影响因子：
--
作者：
Hemingway J;Ranson H;Magill A;Kolaczinski J;Fornadel C;Gimnig J;Coetzee M;Simard F;Roch DK;Hinzoumbe CK;Pickett J;Schellenberg D;Gething P;Hoppé M;Hamon N
通讯作者：
Hamon N
影响因子：
5.5
作者：
Sala, K. A.;Nishiura, H.;Blagborough, A. M.
通讯作者：
Blagborough, A. M.
影响因子：
2.9
作者：
Jaje, Jennifer;Wolcott, Holly N.;Thorpe, Colin
通讯作者：
Thorpe, Colin
影响因子：
3.8
作者：
Silvio M. Zanata;A. C. Luvizon;D. F. Batista;C. M. Ikegami;Fábio O. Pedrosa;Evelise Machado de Souza;Daniela Fojo Seixas Chaves;Luiz Felipe Caron;J. V. Pelizzari;Francisco R.M. Laurindo;Lia S. Nakao
通讯作者：
Silvio M. Zanata;A. C. Luvizon;D. F. Batista;C. M. Ikegami;Fábio O. Pedrosa;Evelise Machado de Souza;Daniela Fojo Seixas Chaves;Luiz Felipe Caron;J. V. Pelizzari;Francisco R.M. Laurindo;Lia S. Nakao
影响因子：
2.4
作者：
JANSE, CJ;MONS, B;VANDERKAAY, HJ
通讯作者：
VANDERKAAY, HJ