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

Zhou CX, Zhou DH, Elsheikha HM, Liu GX, Suo X, Zhu XQ - PLoS ONE (2015)

Bottom Line: The biological significance of these metabolites is discussed.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, PR China; National Animal Protozoa Laboratory and College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Comparison of the mice brain metabolomes during the course of infection.Heat maps representing the significantly changed metabolites between infected groups and the corresponding control groups in ESI+ mode (A, B and C). Normalized metabolite abundance (log2 transformed and row adjustment) are visualized as a color spectrum and the scale from least abundant to highest ranges is from -2.0 to 2.0. Green indicates low expression, whereas red indicates high expression of the detected metabolites. (A) 7D infected group (7I) vs 7D control (7C); (B) 14D infected group (14I) vs 14D control (14C); (C) 21D infected group(21I) vs 21D control (21C).
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pone.0139635.g004: Comparison of the mice brain metabolomes during the course of infection.Heat maps representing the significantly changed metabolites between infected groups and the corresponding control groups in ESI+ mode (A, B and C). Normalized metabolite abundance (log2 transformed and row adjustment) are visualized as a color spectrum and the scale from least abundant to highest ranges is from -2.0 to 2.0. Green indicates low expression, whereas red indicates high expression of the detected metabolites. (A) 7D infected group (7I) vs 7D control (7C); (B) 14D infected group (14I) vs 14D control (14C); (C) 21D infected group(21I) vs 21D control (21C).

Mentions: The differential metabolites associated with toxoplasmosis were identified according to VIP threshold (VIP >1) and the P-value of student’s t-test after FDR correction. These identified metabolites include amino acid, peptide, carbohydrate, lipid, nucleotide, cofactors and vitamins, and are involved in a wide range of biological pathways. The statistically significant metabolites detected at different time points, their m/z values, log2 fold changes (FC) and descriptions are shown in Table 1. Results showed that the number of significantly different metabolites varied during the infection process and only a small set of metabolites exhibited detectable periodic fluctuation nature. On day 7 (R2X = 0.277, R2Y = 0.889, Q2 = -0.837 ESI+; R2X = 0.302, R2Y = 0.927,Q2 = -0.346 ESI-) (Fig 3A), the levels of phosphatidylcholine (PC) (12:0), phosphatidylethanolamine (PE) (18:2), UDP-N-acetyl-D-galactosamine and aconitic acid were found to be higher in the infection group relative to healthy control group, whereas the levels of leukotriene D4 and inosine concentrations were found to be lower (Fig 4A, S2A Fig). Among these metabolites, leukotriene D4 is an important inflammatory mediator, which is formed through a cascade metabolism pathway from arachidonic acid [26].


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

Zhou CX, Zhou DH, Elsheikha HM, Liu GX, Suo X, Zhu XQ - PLoS ONE (2015)

Comparison of the mice brain metabolomes during the course of infection.Heat maps representing the significantly changed metabolites between infected groups and the corresponding control groups in ESI+ mode (A, B and C). Normalized metabolite abundance (log2 transformed and row adjustment) are visualized as a color spectrum and the scale from least abundant to highest ranges is from -2.0 to 2.0. Green indicates low expression, whereas red indicates high expression of the detected metabolites. (A) 7D infected group (7I) vs 7D control (7C); (B) 14D infected group (14I) vs 14D control (14C); (C) 21D infected group(21I) vs 21D control (21C).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4592003&req=5

pone.0139635.g004: Comparison of the mice brain metabolomes during the course of infection.Heat maps representing the significantly changed metabolites between infected groups and the corresponding control groups in ESI+ mode (A, B and C). Normalized metabolite abundance (log2 transformed and row adjustment) are visualized as a color spectrum and the scale from least abundant to highest ranges is from -2.0 to 2.0. Green indicates low expression, whereas red indicates high expression of the detected metabolites. (A) 7D infected group (7I) vs 7D control (7C); (B) 14D infected group (14I) vs 14D control (14C); (C) 21D infected group(21I) vs 21D control (21C).
Mentions: The differential metabolites associated with toxoplasmosis were identified according to VIP threshold (VIP >1) and the P-value of student’s t-test after FDR correction. These identified metabolites include amino acid, peptide, carbohydrate, lipid, nucleotide, cofactors and vitamins, and are involved in a wide range of biological pathways. The statistically significant metabolites detected at different time points, their m/z values, log2 fold changes (FC) and descriptions are shown in Table 1. Results showed that the number of significantly different metabolites varied during the infection process and only a small set of metabolites exhibited detectable periodic fluctuation nature. On day 7 (R2X = 0.277, R2Y = 0.889, Q2 = -0.837 ESI+; R2X = 0.302, R2Y = 0.927,Q2 = -0.346 ESI-) (Fig 3A), the levels of phosphatidylcholine (PC) (12:0), phosphatidylethanolamine (PE) (18:2), UDP-N-acetyl-D-galactosamine and aconitic acid were found to be higher in the infection group relative to healthy control group, whereas the levels of leukotriene D4 and inosine concentrations were found to be lower (Fig 4A, S2A Fig). Among these metabolites, leukotriene D4 is an important inflammatory mediator, which is formed through a cascade metabolism pathway from arachidonic acid [26].

Bottom Line: The biological significance of these metabolites is discussed.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, PR China; National Animal Protozoa Laboratory and College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus