Dissecting erythrocyte invasion mechanisms by the malaria parasite Plasmodium falciparum.

疟疾寄生虫是顶复门中最重要的成员，顶复门是一个巨大且非常成功的细胞内寄生虫群。宿主细胞的入侵允许顶复门寄生虫在一个很大程度上免受宿主防御的小生境中获得丰富的营养源。与许多其他病原体相比，疟原虫属（Plasmodium spp.）可以通过使用它们自己的入侵装置快速进入细胞来识别、穿透和建立自己，从而有效地感染它们的宿主。所有顶复门都采用这种共同的宿主细胞进入模式，但个别物种具有独特的特征，并利用一组特定的配体-受体相互作用。 细胞外疟原虫裂殖子侵入红细胞是一个重要的多步骤过程，快速有效地进入宿主细胞的发展对这些病原体的进化成功至关重要。裂殖子侵入开始于最初的低亲和力附着于红细胞，然后在快速进入之前重新定向以对抗寄生虫顶极与红细胞膜。成功侵入的关键是建立紧密连接，即在红细胞进入过程中沿着侵入裂殖子的长度沿着前进的两个细胞之间的紧密并置点。这个连接为裂殖子入侵马达提供了一个牵引点，使寄生虫能够将自己驱动到红细胞中。随着入侵的进行，红细胞膜向内扩张，形成最初的入侵坑和随后的寄生虫空泡，寄生虫在红细胞内周期期间移动和居住的空间。进入完成时，紧密连接在寄生虫的基部闭合，将空泡和红细胞膜与外部环境密封。我们的实验室有兴趣剖析这个有趣的生物过程背后的机制。

The malaria parasite is the most important member of the Apicomplexa, a large and highly successful group of intracellular parasites. Invasion of host cells allows apicomplexan parasites access to a rich source of nutrients in a niche that is largely protected from host defenses. In contrast to many other pathogenic organisms, Plasmodium spp. can efficiently infect their hosts by rapidly gaining entry to cells using their own invasion apparatus to identify, penetrate, and establish themselves. All Apicomplexa adopt this common mode of host-cell entry but individual species incorporate unique features and utilize a specific set of ligand-receptor interactions. Invasion into an erythrocyte by the extracellular malaria merozoite is an essential multistep process and development of rapid and efficient entry into the host cell has been important in the evolutionary success of these pathogens. Merozoite invasion begins with an initial low affinity attachment to the erythrocyte followed by reorientation to oppose the parasite apical pole with the erythrocyte membrane prior to rapid entry. Critical to successful invasion is the establishment of a tight junction, a point of close apposition between the two cells that progresses along the length of the invading merozoite during erythrocyte entry. This junction provides a point of traction for the merozoite invasion motor, allowing the parasite to drive itself into the erythrocyte. As invasion proceeds the erythrocyte membrane buckles inwards, forming an initial invasion pit and subsequent parasitophorous vacuole, a space into which the parasite moves and resides for the duration of its intraerythrocytic cycle. Entry is completed with the tight junction closing at the base of the parasite, sealing the vacuolar and erythrocyte membranes from the external environment. Our laboratory is interested in dissecting the mechanisms behind this intriguing biological process.