Kafsack Björn F C, Pena Janethe D O, Coppens Isabelle, Ravindran Sandeep, Boothroyd John C, Carruthers Vern B
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Science. 2009 Jan 23;323(5913):530-3. doi: 10.1126/science.1165740. Epub 2008 Dec 18.
Perforin-like proteins are expressed by many bacterial and protozoan pathogens, yet little is known about their function or mode of action. Here, we describe Toxoplasma perforin-like protein 1 (TgPLP1), a secreted perforin-like protein of the intracellular protozoan pathogen Toxoplasma gondii that displays structural features necessary for pore formation. After intracellular growth, TgPLP1-deficient parasites failed to exit normally, resulting in entrapment within host cells. We show that this defect is due to an inability to rapidly permeabilize the parasitophorous vacuole membrane and host plasma membrane during exit. TgPLP1 ablation had little effect on growth in culture but resulted in a reduction greater than five orders of magnitude of acute virulence in mice. Perforin-like proteins from other intracellular pathogens may play a similar role in microbial egress and virulence.
许多细菌和原生动物病原体都会表达穿孔素样蛋白，但对其功能或作用方式却知之甚少。在此，我们描述了弓形虫穿孔素样蛋白1（TgPLP1），这是一种细胞内原生动物病原体刚地弓形虫分泌的穿孔素样蛋白，具有形成孔道所需的结构特征。在细胞内生长后，缺乏TgPLP1的寄生虫无法正常逸出，导致被困在宿主细胞内。我们表明，这种缺陷是由于在逸出过程中无法迅速使寄生泡膜和宿主质膜通透化所致。TgPLP1缺失对体外培养生长影响不大，但导致小鼠急性毒力降低超过五个数量级。来自其他细胞内病原体的穿孔素样蛋白可能在微生物逸出和毒力方面发挥类似作用。
