title: Trypanosoma cruzi Polyamine Transporter: Its Role on Parasite Growth and Survival Under Stress Conditions.
abstract: Trypanosoma cruzi is the etiological agent of Chagas disease, a major health problem in Latin America. Polyamines are polycationic compounds that play a critical role as regulators of cell growth and differentiation. In contrast with other protozoa, T. cruzi is auxotrophic for polyamines because of its inability to synthesize putrescine due to the lack of both, arginine and ornithine decarboxylase; therefore, the intracellular availability of polyamines depends exclusively on transport processes. In this work, the polyamine transporter TcPAT12 was overexpressed in T. cruzi epimastigotes demonstrating that growth rates at different concentrations of polyamines strongly depend on the regulation of the polyamine transport. In addition, parasites overexpressing TcPAT12 showed a highly increased resistance to hydrogen peroxide and the trypanocidal drugs nifurtimox and benznidazole, which act by oxidative stress and interfering the synthesis of polyamine derivatives, respectively. Finally, the presence of putative polyamine transporters was analyzed in T. cruzi, Trypanosoma brucei, and Leishmania major genomes identifying 3-6 genes in these trypanosomatids.
authors.affiliation: Laboratorio de Parasitología Molecular, Instituto de Investigaciones Médicas "Alfredo Lanari", Universidad de Buenos Aires and CONICET, Av. Combatientes de Malvinas 3150, 1427, Buenos Aires, Argentina.
authors.forename: Chantal
authors.initials: C
authors.lastname: Reigada
authors.affiliation: Laboratorio de Parasitología Molecular, Instituto de Investigaciones Médicas "Alfredo Lanari", Universidad de Buenos Aires and CONICET, Av. Combatientes de Malvinas 3150, 1427, Buenos Aires, Argentina.
authors.forename: Melisa
authors.initials: M
authors.lastname: Sayé
authors.affiliation: Laboratorio de Parasitología Molecular, Instituto de Investigaciones Médicas "Alfredo Lanari", Universidad de Buenos Aires and CONICET, Av. Combatientes de Malvinas 3150, 1427, Buenos Aires, Argentina.
authors.forename: Edward Valera
authors.initials: EV
authors.lastname: Vera
authors.affiliation: Instituto de Ciencias y Tecnología "Dr. César Milstein", CONICET, Buenos Aires, Argentina.
authors.forename: Darío
authors.initials: D
authors.lastname: Balcazar
authors.affiliation: Instituto de Ciencias y Tecnología "Dr. César Milstein", CONICET, Buenos Aires, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Fraccaroli
authors.affiliation: Instituto de Ciencias y Tecnología "Dr. César Milstein", CONICET, Buenos Aires, Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Carrillo
authors.affiliation: Laboratorio de Parasitología Molecular, Instituto de Investigaciones Médicas "Alfredo Lanari", Universidad de Buenos Aires and CONICET, Av. Combatientes de Malvinas 3150, 1427, Buenos Aires, Argentina.
authors.forename: Mariana R
authors.initials: MR
authors.lastname: Miranda
authors.affiliation: Laboratorio de Parasitología Molecular, Instituto de Investigaciones Médicas "Alfredo Lanari", Universidad de Buenos Aires and CONICET, Av. Combatientes de Malvinas 3150, 1427, Buenos Aires, Argentina. cpereira@retina.ar.
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Pereira
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001692:Biological Transport; D014355:Chagas Disease / Q000469:parasitology; D015870:Gene Expression; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D010802:Phylogeny; D011073:Polyamines / Q000378:metabolism*; D056510:Position-Specific Scoring Matrices; D013312:Stress, Physiological; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000502:physiology*
chemical_list: D026901:Membrane Transport Proteins; D011073:Polyamines
keywords: Chagas disease; Polyamine transporter; Trypanosoma cruzi