The Toxoplasma protein phosphatase 6 catalytic subunit (TgPP6C) is essential for cell cycle progression and virulence
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Published:2023-12-13
Issue:12
Volume:19
Page:e1011831
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ISSN:1553-7374
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Container-title:PLOS Pathogens
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language:en
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Short-container-title:PLoS Pathog
Author:
Liang Qin-Li,
Nie Lan-Bi,
Elsheikha Hany M.,
Li Ting-Ting,
Sun Li-Xiu,
Zhang Zhi-Wei,
Wang Meng,
Fu Bao-Quan,
Zhu Xing-QuanORCID,
Wang Jin-Lei
Abstract
Protein phosphatases are post-translational regulators of Toxoplasma gondii proliferation, tachyzoite-bradyzoite differentiation and pathogenesis. Here, we identify the putative protein phosphatase 6 (TgPP6) subunits of T. gondii and elucidate their role in the parasite lytic cycle. The putative catalytic subunit TgPP6C and regulatory subunit TgPP6R likely form a complex whereas the predicted structural subunit TgPP6S, with low homology to the human PP6 structural subunit, does not coassemble with TgPP6C and TgPP6R. Functional studies showed that TgPP6C and TgPP6R are essential for parasite growth and replication. The ablation of TgPP6C significantly reduced the synchronous division of the parasite’s daughter cells during endodyogeny, resulting in disordered rosettes. Moreover, the six conserved motifs of TgPP6C were required for efficient endodyogeny. Phosphoproteomic analysis revealed that ablation of TgPP6C predominately altered the phosphorylation status of proteins involved in the regulation of the parasite cell cycle. Deletion of TgPP6C significantly attenuated the parasite virulence in mice. Immunization of mice with TgPP6C-deficient type I RH strain induced protective immunity against challenge with a lethal dose of RH or PYS tachyzoites and Pru cysts. Taken together, the results show that TgPP6C contributes to the cell division, replication and pathogenicity in T. gondii.
Funder
the National Key Research and Development Program of China
the Shanxi Provincial Agricultural and Rural Research Program
the Natural Science Foundation of Gansu Province, China
the Research Funding from Lanzhou Veterinary Research Institute
the State Key Laboratory of Veterinary Etiological Biology
the Fundamental Research Funds of the Chinese Academy of Agricultural Sciences
Publisher
Public Library of Science (PLoS)
Subject
Virology,Genetics,Molecular Biology,Immunology,Microbiology,Parasitology
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