Dissecting erythrocyte invasion mechanisms by the malaria parasite Plasmodium falciparum.

剖析疟疾寄生虫恶性疟原虫的红细胞入侵机制。

• 批准号: 418192-2012
• 负责人: Richard, Dave
• 金额: $ 2.26万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=573526
• 关键词: Dissecting; erythrocyte; invasion; mechanisms; malaria

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.

疟疾寄生虫是顶复门中最重要的成员，顶复门是一个大型且高度成功的细胞内寄生虫群体。入侵宿主细胞使顶复门寄生虫能够在很大程度上免受宿主防御影响的生态位中获得丰富的营养来源。与许多其他病原生物相比，疟原虫属。可以通过使用自己的入侵装置快速进入细胞来识别、渗透和建立自身，从而有效地感染宿主。所有顶端复合体都采用这种进入宿主细胞的常见模式，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。 细胞外疟疾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对于这些病原体的进化成功至关重要。裂殖子入侵开始于最初与红细胞的低亲和力附着，随后在快速进入之前重新定向以与红细胞膜对抗寄生虫顶极。成功入侵的关键是紧密连接的建立，即两个细胞之间的紧密连接点，在红细胞进入过程中沿着入侵裂殖子的长度前进。该连接处为裂殖子入侵运动提供牵引点，使寄生虫能够将自身驱动到红细胞中。随着入侵的进行，红细胞膜向内弯曲，形成最初的入侵坑和随后的寄生液泡，寄生虫在其红细胞内周期期间移动和驻留的空间。进入完成后，寄生虫底部的紧密连接关闭，将液泡和红细胞膜与外部环境隔离。我们的实验室有兴趣剖析这一有趣的生物过程背后的机制。