Global profiling of protein lysine malonylation in Toxoplasma gondii strains of different virulence and genetic backgrounds

Nie, Lan-Bi; Liang, Qin-Li; Wang, Meng; Du, Rui; Zhang, Meng-Yuan; Elsheikha, Hany M.; Zhu, Xing-Quan

Abstract

Lysine malonylation is a post-translational modification (PTM), which regulates many cellular processes. Limited information is available about the level of lysine malonylation variations between Toxoplasma gondii strains of distinct genetic lineages. Yet, insights into such variations are needed to understand the extent to which lysine malonylation contributes to the differences in the virulence and repertoire of virulence factors between T. gondii genotypes. In this study, we profiled lysine malonylation in T. gondii using quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS) and immuno-affinity purification. This analysis was performed on three T. gondii strains with distinctive pathogenicity in mice, including RH strain (type I), PRU strain (type II), and VEG strain (type III). In total, 111 differentially malonylated proteins and 152 sites were upregulated, and 17 proteins and 17 sites were downregulated in RH strain versus PRU strain; 50 proteins and 59 sites were upregu-lated, 50 proteins and 53 sites were downregulated in RH strain versus VEG strain; and 72 proteins and 90 sites were upregulated, and 7 proteins and 8 sites were downregulated in VEG strain versus PRU strain. Differentially malonylated proteins were involved in key processes , such as those mediating the regulation of protein metabolism, stress response, gly-colysis, and actin cytoskeleton. These results reveal an association between lysine malonylation and intra-species virulence differences in T. gondii and offer a new resource for elucidating the contribution of lysine malonylation to energy metabolism and virulence in T. gondii.

Citation

Nie, L., Liang, Q., Wang, M., Du, R., Zhang, M., Elsheikha, H. M., & Zhu, X. (2022). Global profiling of protein lysine malonylation in Toxoplasma gondii strains of different virulence and genetic backgrounds. PLoS Neglected Tropical Diseases, 16(5), Article e0010431. https://doi.org/10.1371/journal.pntd.0010431

• Journal Article Type: Article
• Acceptance Date: Apr 18, 2022
• Online Publication Date: May 16, 2022
• Publication Date: May 16, 2022
• Deposit Date: May 28, 2022
• Publicly Available Date: Jun 1, 2022
• Journal: PLoS Neglected Tropical Diseases
• Electronic ISSN: 1935-2735
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 16
• Issue: 5
• Article Number: e0010431
• DOI: https://doi.org/10.1371/journal.pntd.0010431
• Keywords: Infectious Diseases; Public Health, Environmental and Occupational Health
• Public URL: https://nottingham-repository.worktribe.com/output/8231487
• Publisher URL: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0010431