Publikationsdatum:
2008-12-20
Beschreibung:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662845/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662845/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kafsack, Bjorn F C -- Pena, Janethe D O -- Coppens, Isabelle -- Ravindran, Sandeep -- Boothroyd, John C -- Carruthers, Vern B -- R01 AI021423/AI/NIAID NIH HHS/ -- R01 AI046675/AI/NIAID NIH HHS/ -- R01 AI046675-06/AI/NIAID NIH HHS/ -- R01 AI046675-07/AI/NIAID NIH HHS/ -- R01 AI046675-08/AI/NIAID NIH HHS/ -- R01 AI046675-09/AI/NIAID NIH HHS/ -- R01 AI46675/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 23;323(5913):530-3. doi: 10.1126/science.1165740. Epub 2008 Dec 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19095897" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Amino Acid Sequence
;
Animals
;
Calcimycin/pharmacology
;
Cell Membrane/*metabolism
;
Cell Membrane Permeability
;
Cells, Cultured
;
Host-Parasite Interactions
;
Humans
;
Intracellular Membranes/*metabolism
;
Ionophores/pharmacology
;
Models, Molecular
;
Molecular Sequence Data
;
Perforin/chemistry/genetics/*metabolism
;
Permeability
;
Protein Conformation
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
Protozoan Proteins/chemistry/genetics/*metabolism
;
Toxoplasma/genetics/growth & development/*metabolism/pathogenicity
;
Vacuoles/*metabolism/*parasitology
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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