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Sulfadiazine Sodium Ameliorates the Metabolomic Perturbation in Mice Infected with Toxoplasma gondii
- Source :
- Antimicrobial Agents and Chemotherapy. 63
- Publication Year :
- 2019
- Publisher :
- American Society for Microbiology, 2019.
-
Abstract
- 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 g/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-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. K E Y W O R D S Toxoplasma gondii, biomarkers, metabolomics, mice, serum metabolites, sulfadiazine sodium Toxoplasma gondii, an obligate intracellular protozoan parasite, is highly prevalent in warm-blooded animals and humans (1). T. gondii comprises three clonal lineages (type I, type II, and type III) (2). Despite 98% genetic similarity, dramatic differences in virulence exist among strains belonging to these T. gondii genotypes (3). Humans acquire infection mainly by ingesting undercooked meat containing tissue cysts or oocysts from contaminated water (4). Acute infection with this parasite is mediated by the aggressive, fast-replicating, tachyzoite stage, which can cause encephalitis or retinochoroiditis. In addition, reactivation of the latent form (i.e., bradyzoites-containing cysts) of T. gondii can cause life-threatening conditions and even death in immuno-compromised individuals (5).
- Subjects :
- Purine
Arginine
Metabolite
Administration, Oral
Pharmacology
01 natural sciences
Mice
chemistry.chemical_compound
Tandem Mass Spectrometry
Bio/Medical/Health - Veterinary Medicine
Medicine
Pharmacology (medical)
Chromatography, High Pressure Liquid
Mice, Inbred BALB C
0303 health sciences
biology
Tryptophan
alpha-Linolenic Acid
Valine
Sulfadiazine Sodium
Infectious Diseases
Metabolome
Female
Toxoplasma
Metabolic Networks and Pathways
Antiprotozoal Agents
Sulfadiazine
Glycerophospholipids
03 medical and health sciences
Animals
Humans
Metabolomics
Experimental Therapeutics
030304 developmental biology
Global Research Theme - Health and Wellbeing
business.industry
010401 analytical chemistry
Toxoplasma gondii
Metabolism
medicine.disease
biology.organism_classification
Survival Analysis
Toxoplasmosis
0104 chemical sciences
Pyrimidines
Toxoplasmosis, Animal
chemistry
business
Subjects
Details
- ISSN :
- 10986596 and 00664804
- Volume :
- 63
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy
- Accession number :
- edsair.doi.dedup.....b0e7d5597f8cdbd9701a0a5db2f31062