Iran Biomed J. 2025 Jan 1;29(1 & 2):68-81.
ABSTRACT
BACKGROUND: 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 infectivity under varying environmental conditions. In this study, we integrated metabolomics and transcriptomics data to gain deeper insights into the underlying molecular mechanisms of L. major metacyclogenesis.
METHODS: The metabolic profiles of procyclic and metacyclic promastigotes were first identified using ¹H-NMR spectroscopy. Multivariate statistical analysis revealed 44 significantly different metabolites between the two forms. Metabolic pathway analysis for differentially expressed metabolites identified 10 significantly different pathways (p < 0.05 and impact > 0.05). Finally, the differential gene expression analysis was conducted on transcriptomic data retrieved from public repositories.
RESULT: Results indicated the upregulation of 238 genes and the downregulation of 49 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.
CONCLUSION: 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.
PMID:40223480
