Abstract
Better understanding of the molecular changes associated with disease is essential for identifying new routes to improved therapeutics and diagnostic tests. The aim of this study was to investigate the dynamic changes in the metabolic profile of mouse sera during T. gondii infection. We carried out untargeted metabolomic analysis of sera collected from female BALB/c mice experimentally infected with the T. gondii Pru strain (Genotype II). Serum samples were collected at 7, 14 and 21 day post infection (DPI) from infected and control mice and were subjected to liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS)-based global metabolomics analysis. Multivariate statistical analysis identified 79 differentially expressed metabolites in ESI+ mode and 74 in ESI− mode in sera of T. gondii-infected mice compared to the control mice. Further principal component analysis (PCA) and partial least squares-discrimination analysis (PLS-DA) identified 19 dysregulated metabolites (5 in ESI+ mode and 14 in ESI− mode) related to the metabolism of amino acids and energy metabolism. The potential utility of these metabolites as diagnostic biomarkers was validated through receiver operating characteristic (ROC) curve analysis. These findings provide putative metabolite biomarkers for future study and allow for hypothesis generation about the pathophysiology of toxoplasmosis.
Highlights
Landscape of both the host and parasite during these acute and chronic infections
Metabolomic studies have relied on the use of analytical platforms, such as nuclear magnetic resonance (NMR), gas or liquid chromatography coupled to mass spectrometry (GC-MS/LC-MS) and capillary electrophoresis/mass spectrometry (CE-MS) for the analysis of the metabolome[7]
Our findings indicate that LC-MS-based untargeted metabolomic analysis is able to identify dysregulated metabolites in mouse serum and discriminate the metabolomic profile between T. gondii-infected and non-infected mice, as well as during the different stages of the disease
Summary
Landscape of both the host and parasite during these acute and chronic infections. During chronic infection T. gondii enters a quiescent state; there is a possibility that even the latent parasite stage exerts a considerable impact on the host metabolic profiles[8]. A complete understanding of T. gondii pathogenesis necessitates consideration of the effect of the parasite on the metabolism of body fluids over time In this regard, host serum offers an important window for understanding the biological changes that occur in host during infection. Metabolomic studies have relied on the use of analytical platforms, such as nuclear magnetic resonance (NMR), gas or liquid chromatography coupled to mass spectrometry (GC-MS/LC-MS) and capillary electrophoresis/mass spectrometry (CE-MS) for the analysis of the metabolome[7] Among these techniques, LC/MS has been widely used in metabolites’ identification and quantification, and has been a useful metabolomic method with high sensitivity, peak resolution, and reproducibility[18]. We used LC-Q/TOF-MS-metabolomic-based approach to investigate the impact of T. gondii infection on host metabolism using BALB/c mice as a model To our knowledge, this is the first comprehensive metabolomic analysis of the effect of T. gondii infection on host serum metabolism. The disruption of such pathways reveals the significant impact of T. gondii infection on host metabolic function and may shed light on the molecular mechanisms used by T. gondii to cause disease, as well as those used by host defenses
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