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Induction of Autophagy interferes the tachyzoite to bradyzoite transformation of Toxoplasma gondii



Autophagy process in Toxoplasma gondii plays a vital role in regulating parasite survival or death. Thus, once having an understanding of certain effects of autophagy on the transformation of tachyzoite to bradyzoite this will allow us to elucidate the function of autophagy during parasite development. Herein, we used three TgAtg proteins involved in Atg8 conjugation system, TgAtg3, TgAtg7 and TgAtg8 to evaluate the autophagy level in tachyzoite and bradyzoite of Toxoplasma in vitro based on Pru TgAtg7-HA transgenic strains. We showed that both TgAtg3 and TgAtg8 were expressed at a significantly lower level in bradyzoites than in tachyzoites. Importantly, the number of parasites containing fluorescence-labelled TgAtg8 puncta was significantly reduced in bradyzoites than in tachyzoites, suggesting that autophagy is downregulated in Toxoplasma bradyzoite in vitro. Moreover, after treatment with drugs, bradyzoite-specific gene BAG1 levels decreased significantly in rapamycin-treated bradyzoites and increased significantly in 3-MA-treated bradyzoites in comparison with control bradyzoites, indicating that Toxoplasma autophagy is involved in the transformation of tachyzoite to bradyzoite in vitro. Together, it is suggested that autophagy may serve as a potential strategy to regulate the transformation.


Corresponding author

*Corresponding authors. School of Medical Laboratory Science and School of Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People's Republic of China; Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People's Republic of China. E-mail:;


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Besteiro, S. (2012). Which roles for autophagy in Toxoplasma gondii and related apicomplexan parasites? Molecular and Biochemical Parasitology 184, 18.
Besteiro, S., Brooks, C. F., Striepen, B. and Dubremetz, J. F. (2011). Autophagy protein Atg3 is essential for maintaining mitochondrial integrity and for normal intracellular development of Toxoplasma gondii tachyzoites. PLoS Pathogens 7, e1002416.
Diaz-Troya, S., Perez-Perez, M. E., Florencio, F. J. and Crespo, J. L. (2008). The role of TOR in autophagy regulation from yeast to plants and mammals. Autophagy 4, 851865.
Chen, D., Lin, J., Liu, Y., Li, X., Chen, G., Hua, Q., Nie, Q., Hu, X. and Tan, F. (2016). Identification of TgAtg8–TgAtg3 interaction in Toxoplasma gondii . Acta Tropica 153, 7985.
Geng, J., Klionsky, D. J. (2008). The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. ‘Protein modifications: beyond the usual suspects’ review series. EMBO Reports 9, 859864.
Ghosh, D., Walton, J. L., Roepe, P. D. and Sinai, A. P. (2012). Autophagy is a cell death mechanism in Toxoplasma gondii . Cellular Microbiology 14, 589607.
Gozuacik, D. and Kimchi, A. (2007). Autophagy and cell death. Current Topics in Developmental Biology 78, 217245.
Hua, Q. Q., Li, X. Z., Wan, Y. J., Chen, D., Zhao, X. H., Jiang, K., Hu, X., Pan, C. W. and Tan, F. (2014). Cloning and expression of Toxoplasma gondii autophagy-related protein 3 gene and preparation of its polyclonal antibody. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 32, 432436.
Ichimura, Y., Kirisako, T., Takao, T., Satomi, Y., Shimonishi, Y., Ishihara, N., Mizushima, N., Tanida, I., Kominami, E., Ohsumi, M., Noda, T. and Ohsumi, Y. (2000). A ubiquitin-like system mediates protein lipidation. Nature 408, 488492.
Ichimura, Y., Imamura, Y., Emoto, K., Umeda, M., Noda, T. and Ohsumi, Y. (2004). In vivo and in vitro reconstitution of Atg8 conjugation essential for autophagy. Journal of Biological Chemistry 279, 4058440592.
Kong-Hap, M. A., Mouammine, A., Daher, W., Berry, L., Lebrun, M., Dubremetz, J. F. and Besteiro, S. (2013). Regulation of ATG8 membrane association by ATG4 in the parasitic protist Toxoplasma gondii . Autophagy 9, 13341348.
Kourtis, N. and Tavernarakis, N. (2009). Autophagy and cell death in model organisms. Cell Death and Differentiation 16, 2130.
Kroemer, G., Marino, G. and Levine, B. (2010). Autophagy and the integrated stress response. Molecular Cell 40, 280293.
Laliberte, J. and Carruthers, V. B. (2008). Host cell manipulation by the human pathogen Toxoplasma gondii . Cellular and Molecular Life Sciences 65, 19001915.
Levine, B. and Klionsky, D. J. (2004). Development by self-digestion: molecular mechanisms and biological functions of autophagy. Developmental Cell 6, 463477.
Li, X., Hu, X., Wan, Y., Xie, G., Li, X., Chen, D., Cheng, Z., Yi, X., Liang, S. and Tan, F. (2014). Systematic identification of the lysine succinylation in the protozoan parasite Toxoplasma gondii . Journal of Proteome Research 13, 60876095.
Mao, X. Y., Hua, Q. Q., Li, X. Z., Yao, L. L. and Tan, F. (2014). Preparation and identification of polyclonal antibody against small peptides of beta-tubulin of Toxoplasma gondii . Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 32, 322323.
Mizushima, N., Noda, T., Yoshimori, T., Tanaka, Y., Ishii, T., George, M. D., Klionsky, D. J., Ohsumi, M. and Ohsumi, Y. (1998). A protein conjugation system essential for autophagy. Nature 395, 395398.
Mizushima, N., Yoshimori, T. and Ohsumi, Y. (2011). The role of Atg proteins in autophagosome formation. Annual Review of Cell and Developmental Biology 27, 107132.
Montoya, J. G. and Remington, J. S. (2008). Management of Toxoplasma gondii infection during pregnancy. Clinical Infectious Diseases 47, 554566.
Nakatogawa, H., Ichimura, Y. and Ohsumi, Y. (2007). Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. Cell 130, 165178.
Nakatogawa, H., Suzuki, K., Kamada, Y. and Ohsumi, Y. (2009). Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nature Reviews Molecular Cell Biology 10, 458467.
Ohsumi, Y. and Mizushima, N. (2004). Two ubiquitin-like conjugation systems essential for autophagy. Seminars in Cell and Developmental Biology 15, 231236.
Petiot, A., Ogier-Denis, E., Blommaart, E. F., Meijer, A. J. and Codogno, P. (2000). Distinct classes of phosphatidylinositol 3′-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. Journal of Biological Chemistry 275, 992998.
Picazarri, K., Nakada-Tsukui, K. and Nozaki, T. (2008). Autophagy during proliferation and encystation in the protozoan parasite Entamoeba invadens . Infection and Immunity 76, 278288.
Ponder, E. L. and Bogyo, M. (2007). Ubiquitin-like modifiers and their deconjugating enzymes in medically important parasitic protozoa. Eukaryotic Cell 6, 19431952.
Rigden, D. J., Michels, P. A. and Ginger, M. L. (2009). Autophagy in protists: examples of secondary loss, lineage-specific innovations, and the conundrum of remodeling a single mitochondrion. Autophagy 5, 784794.
Roos, D. S., Donald, R. G., Morrissette, N. S. and Moulton, A. L. (1994). Molecular tools for genetic dissection of the protozoan parasite Toxoplasma gondii . Methods in Cell Biology 45, 2763.
Shpilka, T., Weidberg, H., Pietrokovski, S. and Elazar, Z. (2011). Atg8: an autophagy-related ubiquitin-like protein family. Genome Biology 12, 226.
Sullivan, W. J. and Jeffers, V. (2012). Mechanisms of Toxoplasma gondii persistence and latency. FEMS Microbiology Reviews 36, 717733.
Suvorova, E. S., Radke, J. B., Ting, L. M., Vinayak, S., Alvarez, C. A., Kratzer, S., Kim, K., Striepen, B. and White, M. W. (2013). A nucleolar AAA-NTPase is required for parasite division. Molecular Microbiology 90, 338355. doi:10.1111/mmi.12367.
Tan, F., Hua, Q. Q., Li, X. P., Li, X. Z. and Liang, S. H. (2014). Preparation and application of the polyclonal antibody of Toxoplasma gondii autophagy protein 8 (TgAtg8). Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 32, 130134.
Tanida, I., Mizushima, N., Kiyooka, M., Ohsumi, M., Ueno, T., Ohsumi, Y. and Kominami, E. (1999). Apg7p/Cvt2p: a novel protein-activating enzyme essential for autophagy. Molecular Biology of the Cell 10, 13671379.
Tenter, A. M., Heckeroth, A. R. and Weiss, L. M. (2000). Toxoplasma gondii: from animals to humans. International Journal for Parasitology 30, 12171258.
Weidberg, H., Shvets, E. and Elazar, Z. (2011). Biogenesis and cargo selectivity of autophagosomes. Annual Review of Biochemistry 80, 125156.
Xie, Z., Nair, U. and Klionsky, D. J. (2008). Atg8 controls phagophore expansion during autophagosome formation. Molecular Biology of the Cell 19, 32903298.
Yamaguchi, M., Noda, N. N., Nakatogawa, H., Kumeta, H., Ohsumi, Y. and Inagaki, F. (2010). Autophagy-related protein 8 (Atg8) family interacting motif in Atg3 mediates the Atg3–Atg8 interaction and is crucial for the cytoplasm-to-vacuole targeting pathway. Journal of Biological Chemistry 285, 2959929607.
Yorimitsu, T. and Klionsky, D. J. (2005). Autophagy: molecular machinery for self-eating. Cell Death and Differentiation 12(Suppl. 2), 15421552.



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