title: Metabolomic profiling reveals a finely tuned, starvation-induced metabolic switch inTrypanosoma cruziepimastigotes.
abstract: Trypanosoma cruzi,the etiological agent of Chagas disease, is a protozoan parasite with a complex life cycle involving a triatomine insect and mammals. Throughout its life cycle, theT. cruziparasite faces several alternating events of cell division and cell differentiation in which exponential and stationary growth phases play key biological roles. It is well accepted that arrest of the cell division in the epimastigote stage, both in the midgut of the triatomine insect andin vitro, is required for metacyclogenesis, and it has been previously shown that the parasites change the expression profile of several proteins when entering this quiescent stage. However, little is known about the metabolic changes that epimastigotes undergo before they develop into the metacyclic trypomastigote stage. We applied targeted metabolomics to measure the metabolic intermediates in the most relevant pathways for energy metabolism and oxidative imbalance in exponentially growing and stationary growth-arrested epimastigote parasites. We show for the first time thatT. cruziepimastigotes transitioning from the exponential to the stationary phase exhibit a finely tuned adaptive metabolic mechanism that enables switching from glucose to amino acid consumption, which is more abundant in the stationary phase. This metabolic plasticity appears to be crucial for survival of theT. cruziparasite in the myriad different environmental conditions to which it is exposed during its life cycle.
authors.affiliation: From the Laboratory of Biochemistry of Tryps-LaBTryps, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil.
authors.forename: María Julia
authors.initials: MJ
authors.lastname: Barisón
authors.affiliation: From the Laboratory of Biochemistry of Tryps-LaBTryps, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil.
authors.forename: Ludmila Nakamura
authors.initials: LN
authors.lastname: Rapado
authors.affiliation: the Department of Biochemistry and Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg, Virginia 24061, and.
authors.forename: Emilio F
authors.initials: EF
authors.lastname: Merino
authors.affiliation: From the Laboratory of Biochemistry of Tryps-LaBTryps, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil.
authors.forename: Elizabeth Mieko
authors.initials: EM
authors.lastname: Furusho Pral
authors.affiliation: From the Laboratory of Biochemistry of Tryps-LaBTryps, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil.
authors.forename: Brian Suarez
authors.initials: BS
authors.lastname: Mantilla
authors.affiliation: From the Laboratory of Biochemistry of Tryps-LaBTryps, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil.
authors.forename: Letícia
authors.initials: L
authors.lastname: Marchese
authors.affiliation: the Facultad de Farmacia y Bioquímica, Instituto de Química y Fisicoquímica Biológica (IQUIFIB-CONICET), Universidad de Buenos Aires, 1113 Buenos Aires, Argentina.
authors.forename: Cristina
authors.initials: C
authors.lastname: Nowicki
authors.affiliation: From the Laboratory of Biochemistry of Tryps-LaBTryps, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil, asilber@usp.br.
authors.forename: Ariel Mariano
authors.initials: AM
authors.lastname: Silber
authors.affiliation: the Department of Biochemistry and Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg, Virginia 24061, and maria.cassera@uga.edu.
authors.forename: Maria Belen
authors.initials: MB
authors.lastname: Cassera
mesh_terms: D008018:Life Cycle Stages / Q000502:physiology; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics; D014349:Trypanosoma cruzi / Q000254:growth & development*
keywords: Chagas disease; Trypanosoma cruzi; cell growth; cell metabolism; energy metabolism; epimastigotes; metabolomics; oxidative imbalance