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

Zhou, Chun-Xue; Zhou, Dong‐Hui; Elsheikha, Hany M.; Zhao, Yu; Suo, Xun; Zhu, Xing‐Quan

doi:10.1038/srep19557

Cited by 58 publications

(65 citation statements)

References 47 publications

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“…T. gondii strictly relies on host cellular metabolism to obtain the energy and nutrients for its replication and survival (63). But how T. gondii modulates the metabolism of its host to create a more hospitable metabolic niche remains vague.…”

Section: Discussionmentioning

confidence: 99%

A Human Proteome Array Approach to Identifying Key Host Proteins Targeted by Toxoplasma Kinase ROP18

Yang

Hou

Hao

et al. 2017

Molecular & Cellular Proteomics

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Toxoplasma kinase ROP18 is a key molecule responsible for the virulence of Toxoplasma gondii; however, the mechanisms by which ROP18 exerts parasite virulence via interaction with host proteins remain limited to a small number of identified substrates. To identify a broader array of ROP18 substrates, we successfully purified bioactive mature ROP18 and used it to probe a human proteome array. Sixty eight new putative host targets were identified. Functional annotation analysis suggested that these proteins have a variety of functions, including metabolic process, kinase activity and phosphorylation, cell growth, apoptosis and cell death, and immunity, indicating a pleiotropic role of ROP18 kinase. Among these proteins, four candidates, p53, p38, UBE2N, and Smad1, were further validated. We demonstrated that ROP18 targets p53, p38, UBE2N, and Smad1 for degradation. Importantly, we demonstrated that ROP18 phosphorylates Smad1 Ser-187 to trigger its proteasome-dependent degradation. Further functional characterization of the substrates of ROP18 may enhance understanding of the pathogenesis of Toxoplasma infection and provide new therapeutic targets. Similar strategies could be used to identify novel host targets for other microbial kinases functioning at the pathogen-host interface. Molecular &

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Section: Discussionmentioning

confidence: 99%

A Human Proteome Array Approach to Identifying Key Host Proteins Targeted by Toxoplasma Kinase ROP18

Yang

Hou

Hao

et al. 2017

Molecular & Cellular Proteomics

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“…This pooled sample was used to estimate a mean profile representing all the analytes observed during analysis. The pooled QC sample was injected five times at the beginning of the run to ensure system equilibrium and subsequently every six samples to further monitor the stability of the analysis (Luan et al, ; Zhou et al, ).…”

Section: Methodsmentioning

confidence: 99%

Effects of Tao‐Hong‐Si‐Wu decoction on acute blood stasis in rats based on a LC‐Q/TOF‐MS metabolomics and network approach

Hua

et al. 2017

Biomedical Chromatography

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A novel approach using metabolomics coupled with a metabolic network was used to investigate the effects of Tao-Hong-Si-Wu decoction (THSWD) on the rat model of acute blood stasis syndrome. Acute blood stasis syndrome was induced by placing the rats in ice-cold water following two injections with epinephrine. The hemorheological indicators [whole blood viscosity (WBV) and plasma viscosity (PV)] and the blood coagulation indicators [thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB)] were detected. The nonparametric univariate method and multivariate statistical analysis were performed for determining the potential biomarkers. A correlation map was structured between biochemical indicators and hub metabolites to explain the effects mechanism of THSWD. After the administration of THSWD, the levels of WBV, PV, TT, APTT and FIB returned to levels observed in the control group. According to metabolomics coupled with metabolic network analysis, the intervention of THSWD in rats with acute blood stasis syndrome induced substantial and characteristic changes in their metabolic profiles. Fifteen metabolites were screened, which mainly involved 10 pathways and five hub metabolites, namely, l-glutamate, l-phenylalanine, N-acylsphingosine, arachidonic acid and phosphatidate. The biochemical indicators and hub metabolites could be adjusted to close to normal levels by THSWD. Therefore, combining metabolomics and metabolic network helped to evaluate the effects of THSWD on acute blood stasis.

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“…Urine and plasma samples of Plasmodium bergheiinfected mice showed glycolytic upregulation, increased energy demand, and disrupted gut microbiota (5,(18)(19)(20). Similarly, many intermediates of amino acid and energy metabolism were altered in mouse serum and brain samples after infection with Toxoplasma gondii (21)(22)(23)(24).…”

mentioning

confidence: 99%

Influence of Eimeria falciformis Infection on Gut Microbiota and Metabolic Pathways in Mice

et al. 2018

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Coccidiosis, caused by different species of parasites, is an economically important disease of poultry and livestock worldwide. Here we report previously unknown alterations in the gut microbes and metabolism of BALB/c mice infected with Specifically, we observed a significant shift in the abundance of cecal bacteria and disrupted metabolism in parasitized animals. The relative abundances of bacterium NK4A136,, , and declined in response to infection, whereas, ,, , and were increased. Carbohydrate and amino acid metabolites in the serum samples of infected mice were significantly altered compared to naïve controls. Levels of amino acids, including asparagine, histidine, l-cysteine, tryptophan, lysine, glycine, serine, alanine, proline, ornithine, methionine, and valine, decreased on day 7 postinfection before returning to baseline on day 14. In addition, increased levels of indolelactate and mannitol and a reduced amount of oxalic acid indicated impaired carbon metabolism upon parasitic infection. These data demonstrate that intestinal coccidial infection perturbs the microbiota and disrupts carbon and nitrogen metabolism.

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

Cited by 58 publications

References 47 publications

A Human Proteome Array Approach to Identifying Key Host Proteins Targeted by Toxoplasma Kinase ROP18

A Human Proteome Array Approach to Identifying Key Host Proteins Targeted by Toxoplasma Kinase ROP18

Effects of Tao‐Hong‐Si‐Wu decoction on acute blood stasis in rats based on a LC‐Q/TOF‐MS metabolomics and network approach

Influence of Eimeria falciformis Infection on Gut Microbiota and Metabolic Pathways in Mice

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