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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

OPLS-DA score plot showed a clear separation between the infected brain samples at different time points.(A) The 7 day group and the 14 day group; (B) The 21 day group and the 14 day group; (C) The 21 day group and the 7 day group. In OPLS-DA score plot, each data point represents one mouse brain sample, and the distance between points in the plot indicates the similarity between samples. a. ESI+, b. ESI-. X axis is PC1, y axis is PC2.
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pone.0139635.g005: OPLS-DA score plot showed a clear separation between the infected brain samples at different time points.(A) The 7 day group and the 14 day group; (B) The 21 day group and the 14 day group; (C) The 21 day group and the 7 day group. In OPLS-DA score plot, each data point represents one mouse brain sample, and the distance between points in the plot indicates the similarity between samples. a. ESI+, b. ESI-. X axis is PC1, y axis is PC2.

Mentions: To understand the metabolomic changes in the mice brain during different stages of T. gondii infection, a two-component OPLS-DA model was constructed to achieve a distinct separation between different infection groups (Fig 5). As shown in Table 2, there were many significant alterations in the brain levels of several metabolites, especially between 14 DPI group and 7 DPI group (R2X = 0.77, R2Y = 1, Q2 = 0.892 ESI+; R2X = 0.36, R2Y = 0.962,Q2 = 0.594 ESI-) (Fig 5A). In the positive ion mode, the levels of pantothenic Acid, propionyl-L-carnitine, 3-ketosphingosine, hypoxanthine and inosine were significantly higher in the brain on 14 DPI (Fig 6A). Up-regulated metabolites in negative ion mode included N-Acetylleucine, FMN and ascorbic acid. Meanwhile in the same ion mode, metabolites that were significantly down-regulated included taurine, L-Aspartic acid, ascorbic acid, phosphocholine, γ-aminobutryic acid, o-phosphorylethanolamine, dUTP, N-acetylsphingosine 1-phosphate, choline and acetyl-CoA. Most significantly altered phospholipids were up-regulated no matter in positive ion mode or negative ion mode (Fig 6A, S3A Fig). Only the levels of PC (12:0) and PI (22:2) (log2 fold change:-1.12, -0.74, respectively) were decreased. These results showed that phospholipids anabolism was active during the transitional phase from physical illness to recovery.


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)

OPLS-DA score plot showed a clear separation between the infected brain samples at different time points.(A) The 7 day group and the 14 day group; (B) The 21 day group and the 14 day group; (C) The 21 day group and the 7 day group. In OPLS-DA score plot, each data point represents one mouse brain sample, and the distance between points in the plot indicates the similarity between samples. a. ESI+, b. ESI-. X axis is PC1, y axis is PC2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4592003&req=5

pone.0139635.g005: OPLS-DA score plot showed a clear separation between the infected brain samples at different time points.(A) The 7 day group and the 14 day group; (B) The 21 day group and the 14 day group; (C) The 21 day group and the 7 day group. In OPLS-DA score plot, each data point represents one mouse brain sample, and the distance between points in the plot indicates the similarity between samples. a. ESI+, b. ESI-. X axis is PC1, y axis is PC2.
Mentions: To understand the metabolomic changes in the mice brain during different stages of T. gondii infection, a two-component OPLS-DA model was constructed to achieve a distinct separation between different infection groups (Fig 5). As shown in Table 2, there were many significant alterations in the brain levels of several metabolites, especially between 14 DPI group and 7 DPI group (R2X = 0.77, R2Y = 1, Q2 = 0.892 ESI+; R2X = 0.36, R2Y = 0.962,Q2 = 0.594 ESI-) (Fig 5A). In the positive ion mode, the levels of pantothenic Acid, propionyl-L-carnitine, 3-ketosphingosine, hypoxanthine and inosine were significantly higher in the brain on 14 DPI (Fig 6A). Up-regulated metabolites in negative ion mode included N-Acetylleucine, FMN and ascorbic acid. Meanwhile in the same ion mode, metabolites that were significantly down-regulated included taurine, L-Aspartic acid, ascorbic acid, phosphocholine, γ-aminobutryic acid, o-phosphorylethanolamine, dUTP, N-acetylsphingosine 1-phosphate, choline and acetyl-CoA. Most significantly altered phospholipids were up-regulated no matter in positive ion mode or negative ion mode (Fig 6A, S3A Fig). Only the levels of PC (12:0) and PI (22:2) (log2 fold change:-1.12, -0.74, respectively) were decreased. These results showed that phospholipids anabolism was active during the transitional phase from physical illness to recovery.

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