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Leishmania donovani Induces Multiple Dynamic Responses in the Metabolome Associated with Amastigote Differentiation and Maturation Inside the Human Macrophage

Título : Leishmania donovani Induces Multiple Dynamic Responses in the Metabolome Associated with Amastigote Differentiation and Maturation Inside the Human Macrophage
Autor : Fernández García, Miguel
Mesquita, Inês
Ferreira, Carolina
Araújo, Marta
Saha, Bhaskar
Rey-Stolle, María Fernanda
García Fernández, Antonia
Silvestre, Ricardo
Barbas Arribas, Coral.
Materias: LeishmaniaHost−pathogen interactionsLeishmaniasisMetabolic interactionsMetabolomics
Editorial : American Chemical Society
Citación : Fernández-García M, Mesquita I, Ferreira C, Araújo M, Saha B, Rey-Stolle MF, García A, Silvestre R, Barbas C. Leishmania donovani Induces Multiple Dynamic Responses in the Metabolome Associated with Amastigote Differentiation and Maturation Inside the Human Macrophage. J Proteome Res. 2023 Jul 7;22(7):2256-2270. doi: 10.1021/acs.jproteome.2c00845. Epub 2023 Jun 20. PMID: 37339249.
Resumen : Leishmania donovani infection of macrophages drives profound changes in the metabolism of both the host macrophage and the parasite, which undergoes different phases of development culminating in replication and propagation. However, the dynamics of this parasite-macrophage cometabolome are poorly understood. In this study, a multiplatform metabolomics pipeline combining untargeted, high-resolution CE-TOF/MS and LC-QTOF/MS with targeted LC-QqQ/MS was followed to characterize the metabolome alterations induced in L. donovani-infected human monocyte-derived macrophages from different donors at 12, 36, and 72 h post-infection. The set of alterations known to occur during Leishmania infection of macrophages, substantially expanded in this investigation, characterized the dynamics of the glycerophospholipid, sphingolipid, purine, pentose phosphate, glycolytic, TCA, and amino acid metabolism. Our results showed that only citrulline, arginine, and glutamine exhibited constant trends across all studied infection time points, while most metabolite alterations underwent a partial recovery during amastigote maturation. We determined a major metabolite response pointing to an early induction of sphingomyelinase and phospholipase activities and correlated with amino acid depletion. These data represent a comprehensive overview of the metabolome alterations occurring during promastigote-to-amastigote differentiation and maturation of L. donovani inside macrophages that contributes to our understanding of the relationship between L. donovani pathogenesis and metabolic dysregulation.
Descripción : Este artículo tiene embargado el acceso al texto completo de la versión aceptada hasta el 20 de julio de 2024
URI : http://hdl.handle.net/10637/15428
Derechos: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
ISSN : 1535-3893
Fecha de fin de embargo : 2024-07-20
Fecha de publicación : 7-jul-2023
Centro : Universidad San Pablo-CEU
Aparece en las colecciones: Medicina





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