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Label-Free Quantitative Acetylome Analysis Reveals Toxoplasma gondii Genotype-Specific Acetylomic Signatures

Wang, Ze-Xiang; Hu, Rui-Si; Zhou, Chun-Xue; He, Jun-Jun; M. Elsheikha, Hany; Zhu, Xing-Quan


Ze-Xiang Wang

Rui-Si Hu

Chun-Xue Zhou

Jun-Jun He

Hany M. Elsheikha

Xing-Quan Zhu


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.

Journal Article Type Article
Publication Date Oct 30, 2019
Journal Microorganisms
Electronic ISSN 2076-2607
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 7
Issue 11
Article Number 510
Pages 1-19
APA6 Citation Wang, Z., Hu, R., Zhou, C., He, J., M. Elsheikha, H., & Zhu, X. (2019). Label-Free Quantitative Acetylome Analysis Reveals Toxoplasma gondii Genotype-Specific Acetylomic Signatures. Microorganisms, 7(11), 1-19.
Keywords Toxoplasma gondii; genotype; tachyzoite; acetylation; label-free
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