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Rapid membrane disruption by a perforin-like protein facilitates parasite exit from host cells.

TitleRapid membrane disruption by a perforin-like protein facilitates parasite exit from host cells.
Publication TypeJournal Article
Year of Publication2009
AuthorsKafsack BFC, Pena JDO, Coppens I, Ravindran S, Boothroyd JC, Carruthers VB
JournalScience
Volume323
Issue5913
Pagination530-3
Date Published2009 Jan 23
ISSN1095-9203
KeywordsAmino Acid Sequence, Animals, Calcimycin, Cell Membrane, Cell Membrane Permeability, Cells, Cultured, Host-Parasite Interactions, Humans, Intracellular Membranes, Ionophores, Models, Molecular, Molecular Sequence Data, Perforin, Permeability, Protein Conformation, Protein Structure, Secondary, Protein Structure, Tertiary, Protozoan Proteins, Toxoplasma, Vacuoles
Abstract

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.

DOI10.1126/science.1165740
Alternate JournalScience
PubMed ID19095897
PubMed Central IDPMC2662845
Grant ListR01 AI46675 / AI / NIAID NIH HHS / United States
R01 AI046675-06 / AI / NIAID NIH HHS / United States
R01 AI046675-09 / AI / NIAID NIH HHS / United States
R01 AI046675 / AI / NIAID NIH HHS / United States
R01 AI021423 / AI / NIAID NIH HHS / United States
R01 AI046675-08 / AI / NIAID NIH HHS / United States
R01 AI046675-07 / AI / NIAID NIH HHS / United States

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