Proteomic Differences between Developmental Stages of Toxoplasma gondii Revealed by iTRAQ-Based Quantitative Proteomics

Abstract

Toxoplasma gondii has a complex two-host life-cycle between intermediate host and definitive host. Understanding proteomic variations across the life-cycle stages of T. gondii may improve the understanding of molecular adaption mechanism of T. gondii across life-cycle stages, and should have implications for the development of new treatment and prevention interventions against T. gondii infection. Here, we utilized LC–MS/MS coupled with iTRAQ labeling technology to identify differentially expressed proteins (DEPs) specific to tachyzoite (T), bradyzoites-containing cyst (C) and sporulated oocyst (O) stages of the cyst-forming T. gondii Prugniuad (Pru) strain. A total of 6285 proteins were identified in the three developmental stages of T. gondii. Our analysis also revealed 875, 656, and 538 DEPs in O vs. T, T vs. C, and C vs. O, respectively. The up- and down-regulated proteins were analyzed by Gene Ontology enrichment, KEGG pathway and STRING analyses. Some virulence-related factors and ribosomal proteins exhibited distinct expression patterns across the life-cycle stages. The virulence factors expressed in sporulated oocysts and the number of up-regulated virulence factors in the cyst stage were about twice as many as in tachyzoites. Of the 79 ribosomal proteins identified in T. gondii, the number of up-regulated ribosomal proteins was 33 and 46 in sporulated oocysts and cysts, respectively, compared with tachyzoites. These results support the hypothesis that oocyst and cystic stages are able to adapt to adverse environmental conditions and selection pressures induced by the host's immune response, respectively. These findings have important implications for understanding of the developmental biology of T. gondii, which may facilitate the discovery of novel therapeutic targets to better control toxoplasmosis.

A Double‐Edged Sword: Complement Component 3 in Toxoplasma gondii Infection

“…Interestingly, Wang et al. compared DEPs from different stages of T. gondii Pru strain, including tachyzoite, bradyzoites‐containing cyst, and sporulated oocyst . Moreover, we have previously reported the DEPs of Mongolian gerbil brains infected with T. gondii .…”

Dissection of the in vitro developmental program of Hammondia hammondi reveals a link between stress sensitivity and life cycle flexibility in Toxoplasma gondii

“…Importantly this enrichment becomes more apparent at 15 DPI, indicating that this is not entirely due to residual transcript from the sporozoite stage. Assuming that the majority of these transcript expression differences are manifested at the protein level (which is expected based on multiple studies in T. gondii ; [ Wang et al, 2017 ; Xia et al, 2008 ]), it is exciting to consider what impact these distinct expression profiles might have on parasite development and even the host response. Expression of these T. gondii merozoite-specific genes in H. hammondi zoites may reflect its terminally differentiated state, being infectious only the felid host ( Dubey and Sreekumar, 2003 ).…”

Bioinformatics Analysis of Genes and Pathways of CD11b+/Ly6Cintermediate Macrophages after Renal Ischemia-Reperfusion Injury

“…We created a PPI network to analyse the key genes which regulate other genes. Based on the 927 DEGs in profile 13, PPI was analysed by STRING 10.5 and the cytoHubba app of Cytoscape software (version 3.5.1) as previously described [20] . The combined score of the PPI value was>0.4.…”