Dipartimento Di Malattie Infettive, Istituto Superiore Di Sanità, Rome, Italy.
Servizio Grandi Strumentazioni E Core Facilities, Istituto Superiore Di Sanità, Rome, Italy.
Sci Rep. 2022 Jun 10;12(1):9592. doi: 10.1038/s41598-022-13415-7.
Malaria long-term elimination depends on parasite transmission control. Plasmodium sexual stage maturation in the mosquito, including egress from the host erythrocyte, is one of the prime targets for transmission-blocking interventions. This work aims to identify candidate molecules potentially involved in gamete emergence from the host erythrocyte, as novel transmission blocking targets. We analyzed by quantitative mass spectrometry the proteins released/secreted by purified Plasmodium falciparum gametocytes upon induction of gametogenesis. The proteome obtained showed a good overlap (74%) with the one previously characterized in similar conditions from gametocytes of the rodent malaria parasite P. berghei. Four candidates were selected based on comparative analysis of their abundance values in released vs total gametocyte proteome. We also characterized the P. falciparum orthologue of the microgamete surface protein (MiGS), a marker of male gametocyte secretory vesicles in murine models of malaria. The findings of this study reveal that all the selected candidate proteins are expressed in both genders and localize to vesicle-like structures that respond to gametogenesis stimuli. This result, together with the fact that the selected proteins are released during gamete emergence in both Plasmodium species, makes them interesting candidates for future functional studies to investigate their potential role in the gametogenesis process.
疟疾的长期消除取决于寄生虫传播的控制。疟原虫在蚊子中的有性阶段成熟，包括从宿主红细胞中逸出，是阻断传播干预的主要目标之一。本研究旨在鉴定可能参与从宿主红细胞中逸出配子的候选分子，作为新的传播阻断靶标。我们通过定量质谱分析了在诱导配子发生时，从纯化的恶性疟原虫配子体中释放/分泌的蛋白质。获得的蛋白质组与以前在类似条件下从啮齿动物疟原虫 P. berghei 配子体中得到的蛋白质组有很好的重叠（74%）。基于释放的配子体蛋白与总配子体蛋白中丰度值的比较分析，选择了 4 个候选蛋白。我们还对恶性疟原虫微配子体表面蛋白（MiGS）的同源物进行了表征，MiGS 是疟疾鼠模型中雄性配子体细胞分泌小泡的标志物。本研究的结果表明，所有选定的候选蛋白在两性中都有表达，并定位于对配子发生刺激有反应的囊泡样结构。这一结果，加上所选蛋白在两种疟原虫中都在配子体逸出过程中被释放的事实，使它们成为未来功能研究的有趣候选物，以研究它们在配子发生过程中的潜在作用。
