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

Published online by Cambridge University Press:  01 March 2016

XIANGZHI LI ,
DI CHEN ,
QIANQIAN HUA ,
YUJING WAN ,
LINA ZHENG ,
YANGYANG LIU ,
JIAXIN LIN ,
CHANGWANG PAN ,
XIN HU  and
FENG TAN
XIANGZHI LI
Affiliation:
Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People's Republic of China
DI CHEN
Affiliation:
School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People's Republic of China
QIANQIAN HUA
Affiliation:
Clinical Laboratory, Dongyang People's Hospital, Jinhua, Zhejiang 322100, People's Republic of China
YUJING WAN
Affiliation:
Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People's Republic of China
LINA ZHENG
Affiliation:
Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People's Republic of China
YANGYANG LIU
Affiliation:
School of Medical Laboratory Science and School of Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People's Republic of China
JIAXIN LIN
Affiliation:
School of Medical Laboratory Science and School of Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People's Republic of China
CHANGWANG PAN
Affiliation:
Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People's Republic of China
XIN HU*
Affiliation:
School of Medical Laboratory Science and School of Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People's Republic of China
FENG TAN*
Affiliation:
Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People's Republic of China
*
*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: [email protected]; [email protected]
*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: [email protected]; [email protected]
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Summary

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.

Keywords

Toxoplasma gondiiautophagytransformationtachyzoitebradyzoite
Type
Research Article
Information
Parasitology , Volume 143 , Issue 5 , April 2016 , pp. 639 - 645
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Copyright
Copyright © Cambridge University Press 2016 

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References

REFERENCES

Besteiro, S. (2012). Which roles for autophagy in Toxoplasma gondii and related apicomplexan parasites? Molecular and Biochemical Parasitology 184, 1–8.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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, 851–865.Google Scholar
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, 79–85.Google Scholar
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, 859–864.Google Scholar
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, 589–607.CrossRefGoogle ScholarPubMed
Gozuacik, D. and Kimchi, A. (2007). Autophagy and cell death. Current Topics in Developmental Biology 78, 217–245.Google ScholarPubMed
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, 432–436.Google Scholar
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, 488–492.Google Scholar
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, 40584–40592.Google Scholar
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, 1334–1348.CrossRefGoogle ScholarPubMed
Kourtis, N. and Tavernarakis, N. (2009). Autophagy and cell death in model organisms. Cell Death and Differentiation 16, 21–30.Google ScholarPubMed
Kroemer, G., Marino, G. and Levine, B. (2010). Autophagy and the integrated stress response. Molecular Cell 40, 280–293.Google ScholarPubMed
Laliberte, J. and Carruthers, V. B. (2008). Host cell manipulation by the human pathogen Toxoplasma gondii . Cellular and Molecular Life Sciences 65, 1900–1915.Google Scholar
Levine, B. and Klionsky, D. J. (2004). Development by self-digestion: molecular mechanisms and biological functions of autophagy. Developmental Cell 6, 463–477.Google Scholar
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, 6087–6095.Google Scholar
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, 322–323.Google Scholar
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, 395–398.CrossRefGoogle ScholarPubMed
Mizushima, N., Yoshimori, T. and Ohsumi, Y. (2011). The role of Atg proteins in autophagosome formation. Annual Review of Cell and Developmental Biology 27, 107–132.Google Scholar
Montoya, J. G. and Remington, J. S. (2008). Management of Toxoplasma gondii infection during pregnancy. Clinical Infectious Diseases 47, 554–566.Google Scholar
Nakatogawa, H., Ichimura, Y. and Ohsumi, Y. (2007). Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. Cell 130, 165–178.Google Scholar
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, 458–467.Google Scholar
Ohsumi, Y. and Mizushima, N. (2004). Two ubiquitin-like conjugation systems essential for autophagy. Seminars in Cell and Developmental Biology 15, 231–236.Google Scholar
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, 992–998.Google Scholar
Picazarri, K., Nakada-Tsukui, K. and Nozaki, T. (2008). Autophagy during proliferation and encystation in the protozoan parasite Entamoeba invadens . Infection and Immunity 76, 278–288.Google Scholar
Ponder, E. L. and Bogyo, M. (2007). Ubiquitin-like modifiers and their deconjugating enzymes in medically important parasitic protozoa. Eukaryotic Cell 6, 1943–1952.Google Scholar
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, 784–794.Google Scholar
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, 27–63.Google Scholar
Shpilka, T., Weidberg, H., Pietrokovski, S. and Elazar, Z. (2011). Atg8: an autophagy-related ubiquitin-like protein family. Genome Biology 12, 226.Google Scholar
Sullivan, W. J. and Jeffers, V. (2012). Mechanisms of Toxoplasma gondii persistence and latency. FEMS Microbiology Reviews 36, 717–733.Google Scholar
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, 338–355. doi:10.1111/mmi.12367.Google Scholar
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, 130–134.Google Scholar
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, 1367–1379.Google Scholar
Tenter, A. M., Heckeroth, A. R. and Weiss, L. M. (2000). Toxoplasma gondii: from animals to humans. International Journal for Parasitology 30, 1217–1258.Google Scholar
Weidberg, H., Shvets, E. and Elazar, Z. (2011). Biogenesis and cargo selectivity of autophagosomes. Annual Review of Biochemistry 80, 125–156.Google Scholar
Xie, Z., Nair, U. and Klionsky, D. J. (2008). Atg8 controls phagophore expansion during autophagosome formation. Molecular Biology of the Cell 19, 3290–3298.Google Scholar
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, 29599–29607.CrossRefGoogle ScholarPubMed
Yorimitsu, T. and Klionsky, D. J. (2005). Autophagy: molecular machinery for self-eating. Cell Death and Differentiation 12(Suppl. 2), 1542–1552.Google Scholar