Trypanosoma cruzi: increased proline uptake and oxidative stress

ROCHA SC; MARTÍNEZ SAYÉ M; SILBER AM; PEREIRA CA

Congreso; XXX Reunião Anual da Sociedade Brasileira de Protozoologia; 2014

Sociedade Brasileira de Protozoologia

Trypanosoma cruzi, the etiological agent of Chagas' disease, has a metabolism largely based on the consumption of glucose and proline. Additionally this amino acid is involved in differentiation processes and resistance to several stresses, oxidative, metabolic and osmotic among them. In this work, we studied the importance of proline uptake in oxidative stress and against trypanocidal drugs. We generated a transgenic model of T. cruzi that overexpresses the proline transporter Tc069. These parasites showed a significant increase on the proline transport rate and also had a higher intracellular proline concentration when compared to controls. The uptake was inhibited by all the proline analogues tested, but no by other natural amino acids except D-proline, that competitively inhibited the transport. This lack of stereospecificity results interesting since T. cruzi has two functional proline racemases. We also tested the effect of an increased proline transport in oxidative stress responses (hydrogen peroxide and nitric oxide) and also in trypanocidal drugs resistance (nifurtimox and benznidazol). We found that Tc069 parasites were more resistant than controls in all the cases. Taken together, our results show that decreasing intracellular proline levels, e.g. through blockage of proline transporter Tc069, could affect the survival ability against host natural defenses or pharmacological treatments.