Serum Metabolic Profiling of Oocyst-Induced Toxoplasma gondii Acute and Chronic Infections in Mice Using Mass-Spectrometry

Abstract

Toxoplasma gondii is an obligate intracellular parasite causing severe diseases in immunocompromised individuals and congenitally infected neonates, such as encephalitis and chorioretinitis. This study aimed to determine whether serum metabolic profiling can (i) identify metabolites associated with oocyst-induced T. gondii infection and (ii) detect systemic metabolic differences between T. gondii-infected mice and controls. We performed the first global metabolomics analysis of mice serum challenged with 100 sporulated T. gondii Pru oocysts (Genotype II). Sera from acutely infected mice (11 days post-infection, dpi), chronically infected mice (33 dpi) and control mice were collected and analyzed using LC-MS/MS platform. Following False Discovery Rate filtering, we identified 3871 and 2825 ions in ESI+ or ESI− mode, respectively. Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA) identified metabolomic profiles that clearly differentiated T. gondii-infected and -uninfected serum samples. Acute infection significantly influenced the serum metabolome. Our results identified common and uniquely perturbed metabolites and pathways. Acutely infected mice showed perturbations in metabolites associated with glycerophospholipid metabolism, biosynthesis of amino acid, and tyrosine metabolism. These findings demonstrated that acute T. gondii infection induces a global perturbation of mice serum metabolome, providing new insights into the mechanisms underlying systemic metabolic changes during early stage of T. gondii infection.

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

“…In our previous study, 880 metabolites were altered in mice infected with genotype II T. gondii. These altered metabolites were involved in a range of metabolic pathways, including nucleotides, amino acids, fatty acyls, and central carbon metabolism intermediates (22). In the present study, genotype I parasites altered the abundance of 2,872 metabolites in mouse serum; most of these metabolites belonged common for the acute group versus the control group and the T20 group versus the control group in ESIϩ mode.…”

“…Supernatants were collected, frozen in liquid N 2 for 3 min, and transferred to a Ϫ80°C freezer until analysis. The metabolite extraction was performed as described previously (22). Briefly, serum samples were gradually defrosted by placing the tubes initially at Ϫ20°C for 30 min and then at 4°C.…”

The non-targeted metabolomic profiling of liver reveals the molecular perturbations underlying clonorchiasis

“…Metabolomics provide a powerful method to explore host-parasite interactions and discover the pathogenic mechanism at the biochemical level [21]. Recently, some studies had discovered endogenous metabolites and perturbed metabolic pathways in response to parasite infection [22]. However, it is still unclear whether C.sinensis infection cause metabolic change and dysregulation of biochemical pathways in the liver.…”

Induction and measurement of the early stage of a host‐parasite interaction using a combined optical trapping and Raman microspectroscopy system

“…[1] As T. gondii has the ability to invade the brain, there is still a dire need to better understand the mechanisms by which this parasite crosses the blood-brain-barrier (BBB) and cause brain damage. [3][4][5][6][7] Raman microspectroscopy (RMS) allows sensitive and specific measurement of live cells, whereby vibrational spectra from diffraction-limited sampling volumes can be measured which indicate the presence of endogenous macromolecules, such as proteins, lipids and nucleic acids in cells. [2] Therefore, understanding the metabolic and chemical alterations that accompany T. gondii infection has gained significant attention in the last few years.…”

“…[2] Therefore, understanding the metabolic and chemical alterations that accompany T. gondii infection has gained significant attention in the last few years. [3][4][5][6][7] Raman microspectroscopy (RMS) allows sensitive and specific measurement of live cells, whereby vibrational spectra from diffraction-limited sampling volumes can be measured which indicate the presence of endogenous macromolecules, such as proteins, lipids and nucleic acids in cells. [8] RMS has been used to study the interaction of parasites and host cells, such as Neospora caninum [9] and T. gondii.…”