Trypanosoma cruzi Polyamine Transporter: Its Role on Parasite Growth and Survival Under Stress Conditions
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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.
KeywordsTrypanosoma cruzi Polyamine transporter Chagas disease
Special thanks to Lic. Fabio di Girolamo (IDIM-CONICET) for technical support. This work was supported by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, PIP 2011-0263, and 2013-0664), Agencia Nacional de Promoción Científica y Tecnológica (FONCYT PICT 2012-0559 and 2013-2218). CAP and MRM are members of the career of scientific investigator; CR, MS, and EVV are research fellows from CONICET.
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