Aminzadeh Mansour, Bahrami Fariborz, Piryaei Zeynab, Vasighi Mahdi, Kalantari Zahra, Arjmand Mohammad, Ajdary Soheila
Metabolomics Lab, Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
Department of Immunology, Pasteur Institute of Iran,Tehran, Iran.
Iran Biomed J. 2025 Jan 1;29(1 & 2):68-81. doi: 10.61186/ibj.4899.
Metacyclogenesis is a critical developmental process in the life cycle of Leishmania parasites, particularly in their transition from non-infective procyclic to infective metacyclic promastigotes. This transformation is closely linked to the metabolic adaptation of the parasite, optimizing its survival and study, we integrated metabolomics and transcriptomics data to gain deeper molecular mechanisms of Leishmania major metacyclogenesis.
The metabolic profiles of procyclic and metacyclic promastigotes were first identified using ¹H-NMR spectroscopy. Multivariate statistical analysis conducted to distinguish different metabolites between the two forms. Metabolic pathway analysis was performed using the KEGG database to identify the metabolic pathways that significantly altered and overrepresented in the metabolomic profile. Finally, the differential gene expression and pathway enrichment analyses were conducted on transcriptomic data retrieved from public repositories.
Multivariate statistical analysis revealed that 44 metabolites and ten pathways were significantly different between the two forms. Transcriptome genes during metacyclogenesis. These genes underwent GO and KEGG pathway analyses, revealing upregulated GO categories in the metacyclic phase, including protein phosphorylation, ion transport, signal transduction, and phosphorylation reactions, as well as several downregulated GO categories. Integrating metabolomic and transcriptomic data demonstrated seven significantly different KEGG pathways between procyclic and metacyclic forms, including fructose and mannose, galactose, ascorbate and aldarate, arginine and proline, histidine, inositol phosphate, and pyruvate metabolism.
Our findings suggest distinct metabolic profiles and changes in gene expression associated with the transition from procyclic to metacyclic promastigotes. By integrating diverse omics data, we could identify more reliable altered pathways and biomarkers.
循环前鞭毛体发育是利什曼原虫生命周期中的一个关键发育过程，特别是在其从非感染性的前循环型向感染性的循环型前鞭毛体转变过程中。这种转变与寄生虫的代谢适应密切相关，优化其生存能力。为了深入研究，我们整合了代谢组学和转录组学数据，以深入了解大利什曼原虫循环前鞭毛体发育的分子机制。
首先使用¹H-NMR光谱法鉴定前循环型和循环型前鞭毛体的代谢谱。进行多变量统计分析以区分两种形式之间的不同代谢物。使用KEGG数据库进行代谢途径分析，以确定在代谢组学谱中显著改变和过度代表的代谢途径。最后，对从公共数据库检索到的转录组数据进行差异基因表达和途径富集分析。
多变量统计分析显示，两种形式之间有44种代谢物和10条途径存在显著差异。循环前鞭毛体发育过程中的转录组基因。对这些基因进行了GO和KEGG途径分析，揭示了循环期上调的GO类别，包括蛋白质磷酸化、离子转运、信号转导和磷酸化反应，以及几个下调的GO类别。整合代谢组学和转录组学数据表明，前循环型和循环型之间有7条KEGG途径存在显著差异，包括果糖和甘露糖、半乳糖、抗坏血酸和醛糖酸、精氨酸和脯氨酸、组氨酸、肌醇磷酸和丙酮酸代谢。
我们的研究结果表明，与从前循环型向循环型前鞭毛体转变相关的代谢谱和基因表达存在明显差异。通过整合不同的组学数据，我们可以识别出更可靠的改变途径和生物标志物。
