Artikel ; Online: Proximity biotinylation reveals novel secreted dense granule proteins of Toxoplasma gondii bradyzoites.
2020 Band 15, Heft 5, Seite(n) e0232552
Abstract: Toxoplasma gondii is an obligate intracellular parasite which is capable of establishing life-long chronic infection in any mammalian host. During the intracellular life cycle, the parasite secretes an array of proteins into the parasitophorous vacuole ( ... ...
Abstract | Toxoplasma gondii is an obligate intracellular parasite which is capable of establishing life-long chronic infection in any mammalian host. During the intracellular life cycle, the parasite secretes an array of proteins into the parasitophorous vacuole (PV) where it resides. Specialized organelles called the dense granules secrete GRA proteins that are known to participate in nutrient acquisition, immune evasion, and host cell-cycle manipulation. Although many GRAs have been discovered which are expressed during the acute infection mediated by tachyzoites, little is known about those that participate in the chronic infection mediated by the bradyzoite form of the parasite. In this study, we sought to uncover novel bradyzoite-upregulated GRA proteins using proximity biotinylation, which we previously used to examine the secreted proteome of the tachyzoites. Using a fusion of the bradyzoite upregulated protein MAG1 to BirA* as bait and a strain with improved switch efficiency, we identified a number of novel GRA proteins which are expressed in bradyzoites. After using the CRISPR/Cas9 system to characterize these proteins by gene knockout, we focused on one of these GRAs (GRA55) and found it was important for the establishment or maintenance of cysts in the mouse brain. These findings highlight new components of the GRA proteome of the tissue-cyst life stage of T. gondii and identify potential targets that are important for maintenance of parasite persistence in vivo. |
---|---|
Mesh-Begriff(e) | Animals ; Biotinylation ; Brain/metabolism ; Brain/parasitology ; CRISPR-Cas Systems ; Female ; Gene Knockout Techniques ; Genes, Protozoan ; Humans ; Life Cycle Stages ; Mice ; Mice, Inbred C57BL ; Proteome/metabolism ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism ; Toxoplasma/genetics ; Toxoplasma/growth & development ; Toxoplasma/physiology ; Toxoplasmosis, Animal/metabolism ; Toxoplasmosis, Animal/parasitology ; Toxoplasmosis, Cerebral/metabolism ; Toxoplasmosis, Cerebral/parasitology ; Vacuoles/metabolism ; Virulence |
Chemische Substanzen | Proteome ; Protozoan Proteins |
Sprache | Englisch |
Erscheinungsdatum | 2020-05-06 |
Erscheinungsland | United States |
Dokumenttyp | Journal Article ; Research Support, N.I.H., Extramural |
ZDB-ID | 2267670-3 |
ISSN | 1932-6203 ; 1932-6203 |
ISSN (online) | 1932-6203 |
ISSN | 1932-6203 |
DOI | 10.1371/journal.pone.0232552 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
Zusatzmaterialien
Kategorien
Über subito bestellen
Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.