Sulfadiazine Sodium Improves Dysfunctional Metabolomics in Toxoplasma gondii-infected Mice

ABSTRACT: Toxoplasma gondii is an obligate intracellular protozoan parasite that poses a severe threat to human health, especially those immune-compromised individuals. Sulfadiazine sodium (SDZ) is widely used for the treatment of human toxoplasmosis. However, systems biology researches on the therapeutic effects and mechanisms are not yet well performed. After T. gondii GT1 (Genotype I) infection, BALB/c mice were treated orally with SDZ (250 µg/mL in water) for consecutive 12 days. Mice showed typical acute toxoplasmosis symptoms on day 20 post infection, and 20 percent survived on day 30 post infection and established a chronic infection. An untargeted metabolomics approach based on an UPLC-MS/MS method was employed to identify the serum metabolic changes during SDZ treatment. Multivariate statistical analyses (PCA and PLS-DA) were employed to profile the serum metabolomes from the control mice, acute infection mice and SDZ treated mice. In total, 16,426 metabolite ions could be detected and 14,039 of them were consistently detected in more than 70% of the runs. Our results identified common and uniquely perturbed metabolites and pathways among acutely infected or SDZ treated groups. Acutely infected mice showed a dramatic global metabolic perturbations, and SDZ had a favorable therapeutic effect on parasite-induced acute toxoplasmosis by adjusting the metabolic disorders. Notably, serum metabolomics is proved to be a powerful and reliable approach into the surveillance of disease progression and treatment. More importantly, findings in this study will help provide useful data support for the development of new and safe pharmaceuticals against human toxoplasmosis.

INSTRUMENT(S): Liquid Chromatography Tandem MS (LC-MS/MS)

SUBMITTER: Chun-Xue Zhou 

PROVIDER: MTBLS852 | MetaboLights | 2019-06-18

REPOSITORIES: MetaboLights