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

Science. 2008 Dec 18. [Epub ahead of print]

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

Kafsack BF, Pena JD, Coppens I, Ravindran S, Boothroyd JC, Carruthers VB.

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.

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.

PMID: 19095897 [PubMed - as supplied by publisher]