Trypanosoma cruzi proline transport: its importance in oxidative stress and trypanocidal drugs resistance

SAYE, MELISA; MIRANDA, MARIANA; DI GIROLAMO, FABIO; CAMARA, MARIA DE LOS MILAGROS; PEREIRA, CA

Chascomús

Jornada; XV Jornadas Anuales de la Sociedad Argentina de Biología (SAB); 2013

Sociedad Argentina de Biología (SAB)

Trypanosoma cruzi has a metabolism largely based on the consumption of glucose and proline. L-proline is an important metabolite since it is involved in the differentiation of intracellular epimastigote to trypomastigote forms, which is required for the establishment of infection in the mammalian host. 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 than controls. This transport activity 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 role of proline in oxidative stress responces (hydrogen peroxide and nitric oxide) and also in tripanocidal drugs resistance (nifurtimox and benznidazol). We found that Tc069 parasites were more resistant than controls in all the cases. These results suggest 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.