The Toxoplasma protein phosphatase 6 catalytic subunit (TgPP6C) is essential for cell cycle progression and virulence

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 Quan; 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.

Citation

Liang, Q. L., Nie, L. B., Elsheikha, H. M., Li, T. T., Sun, L. X., Zhang, Z. W., Wang, M., Fu, B. Q., Zhu, X. Q., & Wang, J. L. (2023). The Toxoplasma protein phosphatase 6 catalytic subunit (TgPP6C) is essential for cell cycle progression and virulence. PLoS Pathogens, 19(12), Article e1011831. https://doi.org/10.1371/journal.ppat.1011831

• Journal Article Type: Article
• Acceptance Date: Nov 16, 2023
• Online Publication Date: Dec 13, 2023
• Publication Date: Dec 13, 2023
• Deposit Date: Dec 31, 2023
• Publicly Available Date: Jan 3, 2024
• Journal: PLoS Pathogens
• Print ISSN: 1553-7366
• Electronic ISSN: 1553-7374
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: 12
• Article Number: e1011831
• DOI: https://doi.org/10.1371/journal.ppat.1011831
• Keywords: Tachyzoites; Toxoplasma gondii; Phosphorylation; Parasite replication; Parasitic cell cycles; Centrosomes; Cell cycle and cell division; Phosphoproteins
• Public URL: https://nottingham-repository.worktribe.com/output/29000940
• Publisher URL: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011831
• Additional Information: © 2023 Liang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.