Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Published Online December 18, 2008
Science DOI: 10.1126/science.1165740

Reports

Submitted on September 10, 2008
Accepted on November 17, 2008

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

Björn F.C. Kafsack 1, Janethe D. O. Pena 2, Isabelle Coppens 3, Sandeep Ravindran 4, John C. Boothroyd 4, Vern B. Carruthers 5*

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

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

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 TgPLP1, a secreted perforin-like protein of the intracellular protozoan pathogen Toxoplasma gondii that displays structural features necessary for pore-formation. Following 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 permeabilize rapidly the parasitophorous vacuole membrane and host plasma membrane during exit. TgPLP1 ablation had little effect on growth in culture, but resulted in a >5-order of magnitude reduction of acute virulence in mice. Perforin-like proteins from other intracellular pathogens may play a similar role in microbial egress and virulence.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
'A life or death decision' for pollen tubes in S-RNase-based self-incompatibility.
G. Chen, B. Zhang, Z. Zhao, Z. Sui, H. Zhang, and Y. Xue (2009)
J. Exp. Bot.
   Abstract »    Full Text »    PDF »
Evidence that Human Chlamydia pneumoniae Was Zoonotically Acquired.
G. S. A. Myers, S. A. Mathews, M. Eppinger, C. Mitchell, K. K. O'Brien, O. R. White, F. Benahmed, R. C. Brunham, T. D. Read, J. Ravel, et al. (2009)
J. Bacteriol. 191, 7225-7233
   Abstract »    Full Text »    PDF »
Apicomplexan Parasites Co-Opt Host Calpains to Facilitate Their Escape from Infected Cells.
R. Chandramohanadas, P. H. Davis, D. P. Beiting, M. B. Harbut, C. Darling, G. Velmourougane, M. Y. Lee, P. A. Greer, D. S. Roos, and D. C. Greenbaum (2009)
Science 324, 794-797
   Abstract »    Full Text »    PDF »
Tagging of Endogenous Genes in a Toxoplasma gondii Strain Lacking Ku80.
M.-H. Huynh and V. B. Carruthers (2009)
Eukaryot. Cell 8, 530-539
   Abstract »    Full Text »    PDF »
Infectious disease: parasites poke holes to enable escape.
(2009)
Dis. Model. Mech. 2, 94
   Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)