Translationally controlled tumor protein is required for the fast growth of Toxoplasma gondii and maintenance of its intracellular development

Abstract

Translationally controlled tumor protein (TCTP) is a highly conserved, multifunctional protein that has been implicated in a range of cell physiologic processes, especially cell growth and development. A TCTP-like gene has been identified in the Toxoplasma genome [ Toxoplasma gondii TCTP ( TgTCTP)], although its function remains unknown. The sequence analysis of TgTCTP indicated that it is a highly conserved protein in eukaryotes. We found that the expression level of TgTCTP in the virulent RH strain was significantly higher than that in the avirulent PLK strain. Indirect immunofluorescence showed that TgTCTP was expressed in the parasite cytoplasm. The localization of TgTCTP was unchanged during the replication of the parasite. We expressed a functional recombinant TgTCTP (r TgTCTP) protein in Escherichia coli and found that the recombinant protein could form a multimer. We then evaluated the function of TgTCTP using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 knockout (KO) system. Phenotypic analysis of the KO strain (Δ TgTCTP) revealed that TgTCTP is required for the robust growth of the parasites. TgTCTP deficiency also led to early egress of the parasites and subsequent impairment in their invasion and attachment abilities. We subsequently found that the multimer form of TgTCTP might not be necessary for the growth and replication of the parasite. Then the expression profiling of genes in the Δ TgTCTP and complement strains were analyzed. The results revealed that 988 genes were regulated in Δ TgTCTP compared with the complement strain. Overall, although not essential, TgTCTP is required for the fast growth of Tg and maintenance of its intracellular development.-Zheng, J., Chen, Y., Li, Z., Cao, S., Zhang, Z., Jia, H. Translationally controlled tumor protein is required for the fast growth of Toxoplasma gondii and maintenance of its intracellular development.

Investigating the Role of Translationally Control Tumor Protein in Growth, Development and Differentiation of Dictyostelium discoideum

“…Translationally controlled tumor protein is ubiquitously expressed, highly conserved protein present in various type of cells and tissues implicating its essential role in normal cells. This conservation is also observed in the protozoans, such as Plasmodium, Toxoplasma, and Dictyostelium (Bhisutthibhan et al, 1998;Zheng et al, 2018). It is involved in regulation of cell cycle, development, cytoskeleton, autophagy, and apoptosis.…”

Role of TCTP in Cell Biological and Disease Processes

“…Since the completion of our Special Issue, a few interesting biological activities of TCTP have been reported in non-vertebrate organisms. Some examples are its role in the growth, development and differentiation of the slime mold Dictyostelium discoideum [ 21 ]; the importance in Drosophila for epithelial integrity and organ growth [ 22 ]; and in Toxoplasma gondii for robust growth of the parasite and for the maintenance of its virulence [ 23 ]. Recognizing the importance of TCTP for the survival of unicellular parasites, Bossard et al [ 24 ] took the step to test the efficacy of immunizing mice against the parasitic TCTP of Trypanosoma brucei .…”

Sequence Analysis and Comparison of TCTP Proteins from Human Protozoan Parasites

“…Particularly in human parasites, little is currently known about the functions and processes that involve TCTP orthologs, but some studies have shown that they collaborate in parasite growth, proliferation, reproduction and response to stress conditions, which is why this protein has been suggested as a possible therapeutic target [3][4][5]. Toxoplasma gondii has been reported to require its TCTP ortholog for rapid growth and to maintain its intracellular development [3].…”

“…Particularly in human parasites, little is currently known about the functions and processes that involve TCTP orthologs, but some studies have shown that they collaborate in parasite growth, proliferation, reproduction and response to stress conditions, which is why this protein has been suggested as a possible therapeutic target [3][4][5]. Toxoplasma gondii has been reported to require its TCTP ortholog for rapid growth and to maintain its intracellular development [3]. Moreover, TCTP has been shown to act as an antioxidant and heat shock protein with chaperone activity in some parasites [6][7][8] and can also interact and sequester antiparasitic drugs, thus contributing to the development of resistant strains [9][10][11].…”