Wetzel Dawn M, Schmidt Joann, Kuhlenschmidt Mark S, Dubey J P, Sibley L David
Department of Molecular Microbiology, Campus Box 8230, Washington University School of Medicine, St. Louis, MO 63110, USA.
Infect Immun. 2005 Sep;73(9):5379-87. doi: 10.1128/IAI.73.9.5379-5387.2005.
We examined gliding motility and cell invasion by an early-branching apicomplexan, Cryptosporidium parvum, which causes diarrheal disease in humans and animals. Real-time video microscopy demonstrated that C. parvum sporozoites undergo circular and helical gliding, two of the three stereotypical movements exhibited by Toxoplasma gondii tachyzoites. C. parvum sporozoites moved more rapidly than T. gondii sporozoites, which showed the same rates of motility as tachyzoites. Motility by C. parvum sporozoites was prevented by latrunculin B and cytochalasin D, drugs that depolymerize the parasite actin cytoskeleton, and by the myosin inhibitor 2,3-butanedione monoxime. Imaging of the initial events in cell entry by Cryptosporidium revealed that invasion occurs rapidly; however, the parasite does not enter deep into the cytosol but rather remains at the cell surface in a membrane-bound compartment. Invasion did not stimulate rearrangement of the host cell cytoskeleton and was inhibited by cytochalasin D, even in host cells that were resistant to the drug. Our studies demonstrate that C. parvum relies on a conserved actin-myosin motor for motility and active penetration of its host cell, thus establishing that this is a widely conserved feature of the Apicomplexa.
我们研究了一种早期分支的顶复门原虫——微小隐孢子虫的滑行运动和细胞侵袭，该原虫可导致人和动物的腹泻疾病。实时视频显微镜显示，微小隐孢子虫子孢子会进行圆周运动和螺旋式滑行，这是刚地弓形虫速殖子所表现出的三种典型运动中的两种。微小隐孢子虫子孢子的移动速度比刚地弓形虫子孢子更快，而刚地弓形虫子孢子的运动速度与速殖子相同。微小隐孢子虫子孢子的运动受到拉沙里菌素B和细胞松弛素D的抑制，这两种药物会使寄生虫的肌动蛋白细胞骨架解聚，同时也受到肌球蛋白抑制剂2,3-丁二酮一肟的抑制。对隐孢子虫进入细胞的初始事件进行成像显示，侵袭过程迅速发生；然而，该寄生虫并不会深入细胞质，而是停留在细胞表面的一个膜结合区室中。侵袭并未刺激宿主细胞细胞骨架的重排，并且即使在对该药物有抗性的宿主细胞中，也会受到细胞松弛素D的抑制。我们的研究表明，微小隐孢子虫依靠保守的肌动蛋白-肌球蛋白运动来实现运动和主动穿透宿主细胞，从而证明这是顶复门的一个广泛保守的特征。
