背景:人类非洲锥虫病,通常被称为昏睡病,是一种在撒哈拉以南非洲流行的媒介传播的寄生虫病,由采采蝇传播。苏拉明,具有长期临床使用历史的药物,已经证明了针对布鲁氏锥虫的多种作用方式。本研究采用了全面的工作流程来研究苏拉明对布鲁氏菌的代谢作用,利用多模式代谢组学方法。
目的:本研究的主要目的是使用液相色谱-质谱联用(LC-MS)和核磁共振波谱(NMR)方法全面分析苏拉明对布鲁氏菌的代谢影响。统计分析,包括多变量分析和途径富集分析,用于阐明苏拉明治疗引起的显着变化和代谢变化。
方法:介绍了涉及整合来自LC-MS和NMR技术的高分辨率数据的详细方法。该研究对苏拉明处理和对照布氏木霉样品中的代谢物谱进行了全面分析。统计技术,包括方差分析-同时成分分析(ASCA),主成分分析(PCA),方差分析2,和引导测试,用于辨别苏拉明治疗对代谢组学结果的影响。
结果:我们的研究揭示了对照组和苏拉明治疗组之间代谢谱的显著差异。ASCA和PCA分析证实了MS阴性和NMR分析中这些基团之间的明显分离。此外,方差分析2和自举试验证实了治疗的重要性,时间,以及对代谢组学结果的相互作用影响。对LC-MS数据的功能分析强调了处理对氨基酸的影响,以及氨基糖和核苷酸糖的代谢,同时观察到对碳中介代谢的时间效应(特别是琥珀酸生产途径的糖酵解以及二羧酸和三羧酸(TCA)循环)。
结论:通过将LC-MS和NMR技术与先进的统计分析相结合,这项研究确定了独特的代谢特征和与苏拉明治疗相关的途径。这些发现有助于更深入地了解苏拉明的药理影响,并有可能为开发更有效的非洲锥虫病治疗策略提供信息。
BACKGROUND: Human African trypanosomiasis, commonly known as sleeping sickness, is a vector-borne parasitic disease prevalent in sub-Saharan Africa and transmitted by the tsetse fly.
Suramin, a medication with a long history of clinical use, has demonstrated varied modes of action against Trypanosoma brucei. This study employs a comprehensive workflow to investigate the metabolic effects of
suramin on T. brucei, utilizing a multimodal metabolomics approach.
OBJECTIVE: The primary aim of this study is to comprehensively analyze the metabolic impact of
suramin on T. brucei using a combined liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance spectroscopy (NMR) approach. Statistical analyses, encompassing multivariate analysis and pathway enrichment analysis, are applied to elucidate significant variations and metabolic changes resulting from suramin treatment.
METHODS: A detailed methodology involving the integration of high-resolution data from LC-MS and NMR techniques is presented. The study conducts a thorough analysis of metabolite profiles in both
suramin-treated and control T. brucei brucei samples. Statistical techniques, including ANOVA-simultaneous component analysis (ASCA), principal component analysis (PCA), ANOVA 2 analysis, and bootstrap tests, are employed to discern the effects of suramin treatment on the metabolomics outcomes.
RESULTS: Our investigation reveals substantial differences in metabolic profiles between the control and suramin-treated groups. ASCA and PCA analysis confirm distinct separation between these groups in both MS-negative and NMR analyses. Furthermore, ANOVA 2 analysis and bootstrap tests confirmed the significance of treatment, time, and interaction effects on the metabolomics outcomes. Functional analysis of the data from LC-MS highlighted the impact of treatment on amino-acid, and amino-sugar and nucleotide-sugar metabolism, while time effects were observed on carbon intermediary metabolism (notably glycolysis and di- and tricarboxylic acids of the succinate production pathway and tricarboxylic acid (TCA) cycle).
CONCLUSIONS: Through the integration of LC-MS and NMR techniques coupled with advanced statistical analyses, this study identifies distinctive metabolic signatures and pathways associated with suramin treatment in T. brucei. These findings contribute to a deeper understanding of the pharmacological impact of
suramin and have the potential to inform the development of more efficacious therapeutic strategies against African trypanosomiasis.