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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

The schematic of purine metabolism diagram illustrating the biological significance of some biomarkers for prediction of physical recovery of illness.(□ means that the biomarkers were obtained in this experiment).
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pone.0139635.g007: The schematic of purine metabolism diagram illustrating the biological significance of some biomarkers for prediction of physical recovery of illness.(□ means that the biomarkers were obtained in this experiment).

Mentions: Infected mice began to restore their health on day 14, showing an increased appetite and enhanced mental state. We then investigated metabolites that have the potential to be used as biomarkers for the prediction of physical recovery from acute T. gondii infection. To select potential marker metabolites, differential metabolites identified on the 14 day were subjected to ROC analysis. The differentiation performance (specificity and sensitivity) was assessed by the area under the curve (AUC>0.85) and eight significantly differential metabolites were selected as potential biomarkers, as shown in Table 3. Some marker metabolites are involved in purine metabolism as illustrated in Fig 7.


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)

The schematic of purine metabolism diagram illustrating the biological significance of some biomarkers for prediction of physical recovery of illness.(□ means that the biomarkers were obtained in this experiment).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0139635.g007: The schematic of purine metabolism diagram illustrating the biological significance of some biomarkers for prediction of physical recovery of illness.(□ means that the biomarkers were obtained in this experiment).
Mentions: Infected mice began to restore their health on day 14, showing an increased appetite and enhanced mental state. We then investigated metabolites that have the potential to be used as biomarkers for the prediction of physical recovery from acute T. gondii infection. To select potential marker metabolites, differential metabolites identified on the 14 day were subjected to ROC analysis. The differentiation performance (specificity and sensitivity) was assessed by the area under the curve (AUC>0.85) and eight significantly differential metabolites were selected as potential biomarkers, as shown in Table 3. Some marker metabolites are involved in purine metabolism as illustrated in Fig 7.

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