Global Metabolomic Profiling of Mice Brains following Experimental Infection with the Cyst-Forming Toxoplasma gondii

Zhou, Chun-Xue; Elsheikha, Hany M.; Zhou, Dong-Hui; Liu, Guang-Xue; Suo, Xun; Zhu, Xing-Quan

Abstract

© 2015 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The interplay between the Apicomplexan parasite Toxoplasma gondii and its host has been largely studied. However, molecular changes at the metabolic level in the host central nervous system and pathogenesis-associated metabolites during brain infection are largely unexplored. We used a global metabolomics strategy to identify differentially regulated metabolites and affected metabolic pathways in BALB/c mice during infection with T. gondii Pru strain at 7, 14 and 21 days post-infection (DPI). The non-targeted Liquid Chromatography- Mass Spectrometry (LC-MS) metabolomics analysis detected approximately 2,755 retention time-exact mass pairs, of which more than 60 had significantly differential profiles at different stages of infection. These include amino acids, organic acids, carbohydrates, fatty acids, and vitamins. The biological significance of these metabolites is discussed. Principal Component Analysis and Orthogonal Partial Least Square-Discriminant Analysis showed the metabolites' profile to change over time with the most significant changes occurring at 14 DPI. Correlated metabolic pathway imbalances were observed in carbohydrate metabolism, lipid metabolism, energetic metabolism and fatty acid oxidation. Eight metabolites correlated with the physical recovery from infection-caused illness were identified. These findings indicate that global metabolomics adopted in this study is a sensitive approach for detecting metabolic alterations in T. gondii-infected mice and generated a comparative metabolic profile of brain tissue distinguishing infected from non-infected host.

Citation

Zhou, C., Elsheikha, H., Zhou, D., Liu, G., Suo, X., & Zhu, X. (2015). Global Metabolomic Profiling of Mice Brains following Experimental Infection with the Cyst-Forming Toxoplasma gondii. PLoS ONE, 10(10), https://doi.org/10.1371/journal.pone.0139635

• Journal Article Type: Article
• Acceptance Date: Sep 14, 2015
• Online Publication Date: Oct 2, 2015
• Publication Date: Oct 2, 2015
• Deposit Date: Sep 12, 2017
• Publicly Available Date: Jan 31, 2019
• Journal: PLoS ONE
• Electronic ISSN: 1932-6203
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 10
• Article Number: e0139635
• DOI: https://doi.org/10.1371/journal.pone.0139635
• Public URL: https://nottingham-repository.worktribe.com/output/1111001
• PMID: 00036217