Faculty of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, UK.
Microbiology (Reading). 2023 Aug;169(8). doi: 10.1099/mic.0.001389.
Malaria is an important infectious disease that continues to claim hundreds of thousands of lives annually. The disease is caused by infection of host erythrocytes by apicomplexan parasites of the genus . The parasite contains three different apical organelles - micronemes, rhoptries and dense granules (DGs) - whose contents are secreted to mediate binding to and invasion of the host cell and the extensive remodelling of the host cell that occurs following invasion. Whereas the roles of micronemes and rhoptries in binding and invasion of the host erythrocyte have been studied in detail, the roles of DGs in parasites are poorly understood. They have been proposed to control host cell remodelling through regulated protein secretion after invasion, but many basic aspects of the biology of DGs remain unknown. Here we describe DG biogenesis timing for the first time, using RESA localization as a proxy for the timing of DG formation. We show that DG formation commences approximately 37 min prior to schizont egress, as measured by the recruitment of the DG marker RESA. Furthermore, using a bioinformatics approach, we aimed to predict additional cargo of the DGs and identified the J-dot protein HSP40 as a DG protein, further supporting the very early role of these organelles in the interaction of the parasite with the host cell.
疟疾是一种重要的传染病，每年仍有数十万人因此丧生。这种疾病是由疟原虫属的顶复门寄生虫感染宿主红细胞引起的。寄生虫包含三个不同的顶端细胞器 - 微线体、棒状体和致密颗粒（DG）- 其内容物被分泌出来，介导与宿主细胞的结合和入侵，并在入侵后发生宿主细胞的广泛重塑。虽然微线体和棒状体在宿主红细胞的结合和入侵中的作用已经得到了详细的研究，但 DG 在寄生虫中的作用却知之甚少。有人提出，它们通过入侵后受调控的蛋白质分泌来控制宿主细胞的重塑，但 DG 的许多基本生物学特性仍然未知。在这里，我们首次描述了 DG 的生物发生时间，使用 RESA 定位作为 DG 形成时间的替代物。我们发现，DG 的形成大约在裂殖体外溢前 37 分钟开始，这是通过 DG 标记物 RESA 的募集来衡量的。此外，我们还使用生物信息学方法来预测 DG 的其他货物，并确定 J 点蛋白 HSP40 为 DG 蛋白，这进一步支持了这些细胞器在寄生虫与宿主细胞相互作用中的早期作用。
