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

Zhou, Chun-Xue; Gan, Yunhua; Elsheikha, Hany M.; Chen, Xiaoqing; Cong, Hua; Liu, Qing; Zhu, Xingquan

doi:10.1128/aac.00312-19

Cited by 11 publications

(11 citation statements)

References 43 publications

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“…These drawbacks pose a major obstacle in conventional chemotherapy of toxoplasmosis in humans. To this end, efforts have been made to identify new and more effective medicines [12,13] and to understand the mechanism of action [14] and perturbation associated with the currently used drugs [15].…”

Section: Introductionmentioning

confidence: 99%

Transcriptional changes in Toxoplasma gondii in response to treatment with monensin

Zhai

Elsheikha

et al. 2020

Parasites Vectors

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Background: Infection with the apicomplexan protozoan parasite T. gondii can cause severe and potentially fatal cerebral and ocular disease, especially in immunocompromised individuals. The anticoccidial ionophore drug monensin has been shown to have anti-Toxoplasma gondii properties. However, the comprehensive molecular mechanisms that underlie the effect of monensin on T. gondii are still largely unknown. We hypothesized that analysis of T. gondii transcriptional changes induced by monensin treatment can reveal new aspects of the mechanism of action of monensin against T. gondii.Methods: Porcine kidney (PK)-15 cells were infected with tachyzoites of T. gondii RH strain. Three hours post-infection, PK-15 cells were treated with 0.1 μM monensin, while control cells were treated with medium only. PK-15 cells containing intracellular tachyzoites were harvested at 6 and 24 h post-treatment, and the transcriptomic profiles of T. gondii-infected PK-15 cells were examined using high-throughput RNA sequencing (RNA-seq). Quantitative real-time PCR was used to verify the expression of 15 differentially expressed genes (DEGs) identified by RNA-seq analysis.Results: A total of 4868 downregulated genes and three upregulated genes were identified in monensin-treated T. gondii, indicating that most of T. gondii genes were suppressed by monensin. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of T. gondii DEGs showed that T. gondii metabolic and cellular pathways were significantly downregulated. Spliceosome, ribosome, and protein processing in endoplasmic reticulum were the top three most significantly enriched pathways out of the 30 highly enriched pathways detected in T. gondii. This result suggests that monensin, via down-regulation of protein biosynthesis in T. gondii, can limit the parasite growth and proliferation. Conclusions:Our findings provide a comprehensive insight into T. gondii genes and pathways with altered expression following monensin treatment. These data can be further explored to achieve better understanding of the specific mechanism of action of monensin against T. gondii.

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Section: Introductionmentioning

confidence: 99%

Transcriptional changes in Toxoplasma gondii in response to treatment with monensin

Zhai

Elsheikha

et al. 2020

Parasites Vectors

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“…After elimination and filling in, 4,557 and 5,773 ions were finally obtained. The QC samples were tightly clustered, and were significantly separate from the test samples, indicating that the LC-MS/MS analysis platform had high stability and reproducibility ( 16 ) ( Figures 2C,D ). We further used three-dimensional principal component analysis (PCA) scatter plots to evaluate changes in the metabolite profile of mice during the development of Ang II-induced hypertension.…”

Section: Resultsmentioning

confidence: 99%

“…Peak extraction was mainly achieved using the software Progenesis QI (version 2.2), including peak alignment, peak extraction, normalization, deconvolution, and compound identification. See the previous report for details ( 16 ). The results show the mean ± SEM.…”

Section: Methodsmentioning

confidence: 99%

UPLC-MS-Based Serum Metabolomics Reveals Potential Biomarkers of Ang II-Induced Hypertension in Mice

Yang

Wang

Guo

et al. 2021

Front. Cardiovasc. Med.

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Hypertension is caused by polygenic inheritance and the interaction of various environmental factors. Abnormal function of the renin-angiotensin-aldosterone system (RAAS) is closely associated with changes in blood pressure. As an essential factor in the RAAS, angiotensin II (Ang II) contributes to vasoconstriction and inflammatory responses. However, the effects of overproduction of Ang II on the whole body-metabolism have been unclear. In this study, we established a hypertensive mouse model by micro-osmotic pump perfusion of Ang II, and the maximum systolic blood pressure reached 140 mmHg after 2 weeks. By ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, the metabolites in the serum of hypertensive model and control mice were analyzed. Partial least squares discriminant analysis (PLS-DA) in both positive and negative ionization modes showed clear separation of the two groups. Perfusion of Ang II induced perturbations of multiple metabolic pathways in mice, such as steroid hormone biosynthesis and galactose metabolism. Tandem mass spectrometry revealed 40 metabolite markers with potential diagnostic value for hypertension. Our data indicate that non-targeted metabolomics can reveal biochemical pathways associated with Ang II-induced hypertension. Although researches about the clinical use of these metabolites as potential biomarkers in hypertension is still needed, the current study improves the understanding of systemic metabolic response to sustained release of Ang II in hypertensive mice, providing a new panel of biomarkers that may be used to predict blood pressure fluctuations in the early stages of hypertension.

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“…Metabolomic dysregulation has previously been detected in hosts treated with specific drugs in response to pathogen infections [ 22 , 23 ]. How arginine alters metabolic activities in S. mutans has rarely been studied [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Arginine-induced metabolomic perturbation in Streptococcus mutans

Liu

Zhi

et al. 2022

Journal of Oral Microbiology

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Background Streptococcus mutans is a major pathogen responsible for dental caries. Arginine is a promising potential caries preventive agent which can inhibit the growth of S. mutans . However, the mechanism whereby arginine inhibits S. mutans growth remains unclear. Aim To assess the impact of arginine-induced metabolomic perturbations on S. mutans under biofilm conditions. Methods We identified 5,933 and 7,413 ions in positive (ESI+) and negative (ESI-) electrospray ion modes, respectively, with a total of 11.05% and 11.58% differential ions subsequently detected in two respective modes. Further analyses of these metabolites led to identification of 8 and 22 metabolic pathways that were affected by arginine treatment in ESI+ and ESI- modes., Results Once or twice daily treatments of S. mutans biofilms with arginine resulted in reductions in biofilm biomass. Significant reductions in EPS production were observed following twice daily arginine treatments. Identified metabolites that were significantly differentially abundant following arginine treatment were associated with glycolysis metabolism, amino sugar and nucleotide sugar metabolism, and peptidoglycan synthesis. Conclusions Arginine can reduce S. mutans biofilm growth and acid production by inhibiting glycolysis, amino sugar and nucleotide sugar metabolism, and peptidoglycan synthesis.

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

Cited by 11 publications

References 43 publications

Transcriptional changes in Toxoplasma gondii in response to treatment with monensin

Transcriptional changes in Toxoplasma gondii in response to treatment with monensin

UPLC-MS-Based Serum Metabolomics Reveals Potential Biomarkers of Ang II-Induced Hypertension in Mice

Arginine-induced metabolomic perturbation in Streptococcus mutans

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