Abstract
Distinct genotypic and pathogenic differences exist between Toxoplasma gondii genotypes. For example, genotype I is highly virulent, whereas genotype II and genotype III are less virulent. Moreover, Chinese 1 genotype (ToxoDB#9) is also virulent. Here, we compare the acetylomes of genotype 1 (RH strain) and Chinese 1 genotype (ToxoDB#9, PYS strain) of T. gondii. Using mass spectrometry enriched for acetylated peptides, we found a relationship between the levels of protein acetylation and parasite genotype-specific virulence. Notably, lysine acetylation was the largest (458 acetylated proteins) in RH strain, followed by PYS strain (188 acetylated proteins), whereas only 115 acetylated proteins were detected in PRU strain. Our analysis revealed four, three, and four motifs in RH strain, PRU strain and PYS strain, respectively. Three conserved sequences around acetylation sites, namely, xxxxxKAcHxxxx, xxxxxKAcFxxxx, and xxxxGKAcSxxxx, were detected in the acetylome of the three strains. However, xxxxxKAcNxxxx (asparagine) was found in RH and PYS strains but was absent in PRU strain. Our analysis also identified 15, 3, and 26 differentially expressed acetylated proteins in RH strain vs. PRU strain, PRU strain vs. PYS strain and PYS strain vs. RH strain, respectively. KEGG pathway analysis showed that a large proportion of the acetylated proteins are involved in metabolic processes. Pathways for the biosynthesis of secondary metabolites, biosynthesis of antibiotics and microbial metabolism in diverse environments were featured in the top five enriched pathways in all three strains. However, acetylated proteins from the virulent strains (RH and PYS) were more enriched in the pyruvate metabolism pathway compared to acetylated proteins from PRU strain. Increased levels of histone-acetyl-transferase and glycyl-tRNA synthase were detected in RH strain compared to PRU strain and PYS strain. Both enzymes play roles in stress tolerance and proliferation, key features in the parasite virulence. These findings reveal novel insight into the acetylomic profiles of major T. gondii genotypes and provide a new important resource for further investigations of the roles of the acetylated parasite proteins in the modulation of the host cell response to the infection of T. gondii.
Highlights
Toxoplasma gondii is an apicomplexan protozoan parasite which has caused significant morbidity and mortality worldwide [1]
In an effort to partially address this research need and improve the understanding of the molecular mechanisms underpinning pathogenicity differences between genotypes of T. gondii, we studied the acetylomes of three T. gondii strains belonging to different genotypes, namely RH strain, PRU strain and PYS (Chinese 1) strain
We investigated the differences in the level of lysine acetylation within T. gondii genotypes using label-free quantitative acetylomics
Summary
Toxoplasma gondii is an apicomplexan protozoan parasite which has caused significant morbidity and mortality worldwide [1]. This parasite can infect most vertebrate species, including mammals, birds, and humans. In immune-competent individuals, infection with T. gondii is usually asymptomatic or causes latent infection. T. gondii exhibits a complex life-cycle, which includes the asexual reproductive phase occurring in the intermediate host and sexual phase that occurs in the intestine of the definitive feline host. The asexual reproduction results in the formation of fast-replicating tachyzoites, which play a key role in the dissemination of T. gondii infection during acute infection. The sexual reproduction in the feline intestine ends up with the formation and shedding of environmentally resistant oocysts
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
