Metabolomic Profiling of Mice Serum during Toxoplasmosis Progression Using Liquid Chromatography-Mass Spectrometry

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.