Dogga, Sunil Kumar and Lunghi, Matteo and Maco, Bohumil and Li, Jiagui and Claudi, Beatrice and Marq, Jean-Baptiste and Chicherova, Natalia and Kockmann, Tobias and Bumann, Dirk and Hehl, Adrian B. and Soldati-Favre, Dominique and Hammoudi, Pierre-Mehdi. (2022) Importance of aspartyl protease 5 in the establishment of the intracellular niche during acute and chronic infection of Toxoplasma gondii. Molecular Microbiology, 118 (6). pp. 601-622.
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Abstract
Virulence and persistence of the obligate intracellular parasite Toxoplasma gondii involve the secretion of effector proteins belonging to the family of dense granule proteins (GRAs) that act notably as modulators of the host defense mechanisms and participate in cyst wall formation. The subset of GRAs residing in the parasitophorous vacuole (PV) or exported into the host cell, undergo proteolytic cleavage in the Golgi upon the action of the aspartyl protease 5 (ASP5). In tachyzoites, ASP5 substrates play central roles in the morphology of the PV and the export of effectors across the translocon complex MYR1/2/3. Here, we used N-terminal amine isotopic labeling of substrates to identify novel ASP5 cleavage products by comparing the N-terminome of wild-type and Δasp5 lines in tachyzoites and bradyzoites. Validated substrates reside within the PV or PVM in an ASP5-dependent manner. Remarkably, Δasp5 bradyzoites are impaired in the formation of the cyst wall in vitro and exhibit a considerably reduced cyst burden in chronically infected animals. More specifically two-photon serial tomography of infected mouse brains revealed a comparatively reduced number and size of the cysts throughout the establishment of persistence in the absence of ASP5.
Faculties and Departments: | 05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Bumann) |
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UniBasel Contributors: | Bumann, Dirk and Li, Jiagui and Claudi, Beatrice |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | Blackwell |
ISSN: | 0950-382X |
e-ISSN: | 1365-2958 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Language: | English |
Identification Number: |
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edoc DOI: | |
Last Modified: | 07 Mar 2023 11:24 |
Deposited On: | 07 Mar 2023 11:23 |
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