Proteomics analysis reveals that the proto-oncogene eIF-5A indirectly influences the growth, invasion and replication of Toxoplasma gondii tachyzoite

• Published in: Parasites & vectors Vol. 14; no. 1; pp. 283 - 14
• Main Authors: Liu, Xinchao, Li, Chunjing, Li, Xiaoyu, Ehsan, Muhammad, Lu, Mingmin, Li, Ke, Xu, Lixin, Yan, Ruofeng, Song, Xiaokai, Li, XiangRui
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26.05.2021; BioMed Central; BMC
• Subjects: Animals; Antigens; Cancer; Cell growth; Cell proliferation; Cell surface; Cloning; CRISPR-Cas Systems; DNA Replication; Drug development; EIF-5A; Enzymes; Eukaryotic Translation Initiation Factor 5A; Female; Gene Deletion; Genes; Genetic aspects; Host-parasite relationships; Invasion; Medical research; Mice; Mice, Inbred BALB C; Multiplication; Oncogenes; Parasites; Parasitological research; Pathogenesis; Peptide Initiation Factors - genetics; Peptide Initiation Factors - metabolism; Physiological aspects; Plasmids; Protein Interaction Maps; Protein synthesis; Proteins; Proteomics; Proteomics - methods; Proto-oncogenes; Proto-Oncogenes - genetics; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Rats; Rats, Sprague-Dawley; Replication; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Survival; Tachyzoites; Toxoplasma; Toxoplasma - genetics; Toxoplasma - physiology; Toxoplasma gondii; Toxoplasmosis - parasitology; Translation elongation factors; Virulence; China; United States > US; Replication; Toxoplasma gondii; EIF-5A; Invasion
• ISSN: 1756-3305; 1756-3305
• DOI: 10.1186/s13071-021-04791-6

The proliferative stage (tachyzoite) of Toxoplasma gondii (T. gondii) is critical for its transmission and pathogenesis, and a proto-oncogene eukaryotic translation initiation factor (eIF-5A) plays an important role in various cellular processes such as cell multiplication. We performed a proteomic study to evaluate the specific roles of eIF-5A involved in invasion and replication of T. gondii, and both in vivo and in vitro trials using eIF-5A-interfered and wild tachyzoites were performed to verify the proteomic results. The results of our study showed that T. gondii eIF-5A affected tachyzoite growth and also participated in the synthesis of proteins through regulation of both ribosomal and splicing pathways. Inhibition of eIF-5A in T. gondii resulted in the downregulated expression of soluble adhesions, such as microneme protein 1 (MIC1) and MIC4, which in turn decreased the parasite population that adhered to the surface of host cells. The reduced attachment, combined with lower expression of some rhoptry proteins (ROPs) and dense granule antigens (GRAs) involved in different stages of T. gondii invasion such as ROP4 and GRA3, ultimately reduce the invasion efficiency. These processes regulated by eIF-5A eventually affect the replication of tachyzoites. Our findings showed that eIF-5A influenced tachyzoite survival and was also involved in the process of parasite invasion and replication. These results will provide new clues for further development of targeted drugs to control T. gondii infection.