Sulfadiazine Sodium Ameliorates the Metabolomic Perturbation in Mice Infected with Toxoplasma gondii.

In this study, we analyzed the global metabolomic changes associated with Toxoplasma gondii infection in mice in the presence or absence of sulfadiazine sodium (SDZ) treatment. BALB/c mice were infected with T. gondii GT1 strain and treated orally with SDZ (250 μg/ml in water) for 12 consecutive days. Mice showed typical manifestations of illness at 20 days postinfection (dpi); by 30 dpi, 20% had survived and developed latent infection. We used ultraperformance liquid chromatography-mass spectrometry to profile the serum metabolomes in control (untreated and uninfected) mice, acutely infected mice, and SDZ-treated and infected mice. Infection induced significant perturbations in the metabolism of α-linolenic acid, purine, pyrimidine, arginine, tryptophan, valine, glycerophospholipids, and fatty acyls. However, treatment with SDZ seemed to alleviate the serum metabolic alterations caused by infection. The restoration of the serum metabolite levels in the treated mice was associated with better clinical outcomes. These data indicate that untargeted metabolomics can reveal biochemical pathways associated with restoration of the metabolic status of T. gondii-infected mice following SDZ treatment and could be used to monitor responses to SDZ treatment. This study provides a new systems approach to elucidate the metabolic and therapeutic effects of SDZ in the context of murine toxoplasmosis.