2009年1月23日发布的《科学》（Science）封面文章由密歇根大学医学院微生物与免疫学系，约翰霍普金斯大学公共卫生学院分子微生物与免疫学系，巴西Federal de Uberlandia大学免疫学系和斯坦福大学医学院微生物与免疫学系的科学家提供。

文章通讯作者是密歇根大学医学院的Vern B.Carruthers副教授，主要研究寄生虫的感染机制，尤其是寄生虫侵入细胞和逃避免疫攻击的机制。

在《科学》的这篇封面文章中，研究者主要解释了寄生虫的一个穿孔素样蛋白（Perforin-Like Protein）在寄生虫成熟后穿破细胞膜从细胞中释放出来的过程中所起的作用。

多种细菌和原生动物类的生物体都能表达穿孔素样蛋白，但是这个蛋白的功能和作用模式却一直不为人所知。在本篇文章中，研究者将以鼠弓形虫为研究对象，研究弓形虫穿孔素样蛋白TgPLP1的结构特征和功能。弓形虫是一种胞内寄生虫，一般来说，弓形虫在成熟后生成裂殖子离开细胞，而攻击附近的新细胞，如果穿孔素样蛋白TgPLP1缺陷则会导致成熟的弓形虫无法破坏细胞膜而出芽，这样弓形虫就会遭到宿主的免疫细胞攻击。研究发现，TgPLP1缺陷会导致弓形虫无法对寄生泡和细胞膜的透化处理，也就无法离开细胞。缺失TgPLP1对弓形虫的生长没有太大的影响，但是对弓形虫的毒力有一定的影响。

研究者认为，其他的胞内寄生生物（细菌，病毒，寄生虫）的穿孔素样蛋白可能也有相似的功能作用。

推荐原始出处：

Science，DOI: 10.1126/science.1165740，Bj?rn F. C. Kafsack，Vern B. Carruthers

Rapid Membrane Disruption by a Perforin-Like Protein Facilitates Parasite Exit from Host Cells

Bj?rn F. C. Kafsack,1,2 Janethe D. O. Pena,3 Isabelle Coppens,2 Sandeep Ravindran,4 John C. Boothroyd,4 Vern B. Carruthers1*

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.

1 Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
2 Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
3 Department of Immunology, Universidade Federal de Uberlandia, Uberlandia, Brazil.
4 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.