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Originally published in Science Express on 18 December 2008
Science 23 January 2009:
Vol. 323. no. 5913, pp. 530 - 533
DOI: 10.1126/science.1165740
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Reports

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

Björn 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.

* To whom correspondence should be addressed. E-mail: vcarruth{at}umich.edu

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