Plasmodium female gamete surface HSP90 is a key determinant for fertilization.
Plasmodium female gamete surface HSP90 is a key determinant for fertilization.
复制标题
疟原虫雌配子表面 HSP90 是受精的关键决定因素。
DOI：
10.1128/mbio.03142-23
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发表时间：
2024
期刊：
影响因子：
6.4
通讯作者：
Jacobs-Lorena,Marcelo
中科院分区：
文献类型：
--
作者：
Cha,Sung-Jae;Vega-Rodriguez,Joel;Tao,Dingyin;Kudyba,HeatherM;Hanner,Kelly;Jacobs-Lorena,Marcelo
疟原虫受精是疟原虫在蚊子体内发育的一个重要步骤，也是阻断病原体传播的主要目标。使用噬菌体肽展示筛选，我们确定了MG 1，一种结合到男性配子和抑制受精的肽，可能是通过与女性配子配体竞争。抗MG 1抗体结合到雌性配子表面，并通过这样做，也抑制受精。我们确定该抗体识别疟原虫雌配子表面的HSP 90。我们的研究结果确立了疟原虫HSP 90作为开发阻断传播疫苗的主要靶点。重要的是，疟疾每年导致50多万人死亡，而且近年来这一数字没有下降。迫切需要开发防治这一疾病的新工具。在这篇文章中，我们报告了一个关键的分子-HSP 90-在寄生虫的雌配子的表面上，需要受精发生和完成寄生虫在蚊子的周期。HSP 90是一种很有希望的阻断传播疫苗的候选者。
Plasmodiumfertilization, an essential step for the development of the malaria parasite in the mosquito, is a prime target for blocking pathogen transmission. Using phage peptide display screening, we identified MG1, a peptide that binds to male gametes and inhibits fertilization, presumably by competing with a female gamete ligand. Anti-MG1 antibodies bind to the female gamete surface and, by doing so, also inhibit fertilization. We determined that this antibody recognizes HSP90 on the surface ofPlasmodiumfemale gametes. Our findings establishPlasmodiumHSP90 as a prime target for the development of a transmission-blocking vaccine.IMPORTANCEMalaria kills over half a million people every year and this number has not decreased in recent years. The development of new tools to combat this disease is urgently needed. In this article, we report the identification of a key molecule—HSP90—on the surface of the parasite’s female gamete that is required for fertilization to occur and for the completion of the parasite cycle in the mosquito. HSP90 is a promising candidate for the development of a transmission-blocking vaccine.