Abstract
BackgroundThe 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.MethodsWe 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.ResultsThe 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.ConclusionsOur 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.Graphical abstract
Highlights
The proliferative stage of Toxoplasma gondii (T. gondii) is critical for its transmission and pathogenesis, and a proto-oncogene eukaryotic translation initiation factor plays an important role in various cellular processes such as cell multiplication
Our results provide a potential source for understanding the role of eukaryotic translation initiation factor 5A (eIF-5A) during T. gondii pathogenesis, which will aid in controlling toxoplasmosis in the near future
Results eIF‐5A gene essential for T. gondii survival In order to study the biological functions of TgeIF5A, the CRISPR/Cas9 system was used as an efficient gene deletion method
Summary
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. Tachyzoites are characterized by a rapidly growing stage during the acute phase of infection in host cells, perpetuating the lytic cycle via host cell invasion, intracellular replication and parasite egress. Replication is the most critical process in parasite physiology and pathogenesis of T. gondii [6, 7], and host cell invasion is the prerequisite for tachyzoite replication. Invasion of host cells by T. gondii is a multistep process accompanied by secretion of numerous regulated proteins from three distinct parasite organelles called micronemes, rhoptries and dense granules [8]. The concentration of rhoptries and dense granules has been associated with the formation of a specialized parasitophorous vacuole (PV) [11, 12], which results in parasite internalization through the endocytic pathway [6]
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