title: A Multiplatform Metabolomic Approach to the Basis of Antimonial Action and Resistance in Leishmania infantum.
abstract: There is a rising resistance against antimony drugs, the gold-standard for treatment until some years ago. That is a serious problem due to the paucity of drugs in current clinical use. In a research to reveal how these drugs affect the parasite during treatment and to unravel the underlying basis for their resistance, we have employed metabolomics to study treatment in Leishmania infantum promastigotes. This was accomplished first through the untargeted analysis of metabolic snapshots of treated and untreated parasites both resistant and responders, utilizing a multiplatform approach to give the widest as possible coverage of the metabolome, and additionally through novel monitoring of the origin of the detected alterations through a 13C traceability experiment. Our data stress a multi-target metabolic alteration with treatment, affecting in particular the cell redox system that is essential to cope with detoxification and biosynthetic processes. Additionally, relevant changes were noted in amino acid metabolism. Our results are in agreement with other authors studying other Leishmania species.
authors.affiliation: Centro de Metabolomica y Bioanalisis (CEMBIO), Unidad Asociada Interacciones, Metabolismo y Bioanálisis CSIC-CEU, Facultad de Farmacia, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, 28668, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Rojo
authors.affiliation: Centro de Metabolomica y Bioanalisis (CEMBIO), Unidad Asociada Interacciones, Metabolismo y Bioanálisis CSIC-CEU, Facultad de Farmacia, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, 28668, Madrid, Spain; Institute of Chemistry, University of São Paulo (USP), Campus São Paulo, São Paulo, 05508-000, São Paulo, Brazil.
authors.forename: Gisele A B
authors.initials: GA
authors.lastname: Canuto
authors.affiliation: Centro de Metabolomica y Bioanalisis (CEMBIO), Unidad Asociada Interacciones, Metabolismo y Bioanálisis CSIC-CEU, Facultad de Farmacia, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, 28668, Madrid, Spain; Colegiado de Medicina, Universidade Federal do Amapá, Macapá, AP, Brazil.
authors.forename: Emerson A
authors.initials: EA
authors.lastname: Castilho-Martins
authors.affiliation: Institute of Chemistry, University of São Paulo (USP), Campus São Paulo, São Paulo, 05508-000, São Paulo, Brazil.
authors.forename: Marina F M
authors.initials: MF
authors.lastname: Tavares
authors.affiliation: Centro de Metabolomica y Bioanalisis (CEMBIO), Unidad Asociada Interacciones, Metabolismo y Bioanálisis CSIC-CEU, Facultad de Farmacia, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, 28668, Madrid, Spain.
authors.forename: Coral
authors.initials: C
authors.lastname: Barbas
authors.affiliation: Centro de Metabolomica y Bioanalisis (CEMBIO), Unidad Asociada Interacciones, Metabolismo y Bioanálisis CSIC-CEU, Facultad de Farmacia, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, 28668, Madrid, Spain.
authors.forename: Ángeles
authors.initials: Á
authors.lastname: López-Gonzálvez
authors.affiliation: Centro de Investigaciones Biológicas (CSIC), Unidad Asociada Interacciones, Metabolismo y Bioanálisis CSIC-CEU, Ramiro de Maeztu 9, 28040, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Rivas
mesh_terms: D000965:Antimony / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002853:Chromatography, Liquid / Q000379:methods; D004351:Drug Resistance; D006801:Humans; D018314:Leishmania infantum / Q000187:drug effects* / Q000378:metabolism; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000981:Antiprotozoal Agents; D000965:Antimony