Expressão heteróloga de catalase e resistência ao estresse oxidativo em Trypanosoma cruzi

Abstract

Trypanosoma cruzi, the causal agent of Chagas disease, is exposed to oxidative stress situations during its complex life cycle. To deal with these stresses, one of the strategies employed by this parasite for hydroperoxides detoxification is a peculiar trypanothione-dependent antioxidant system. However, T. cruzi's antioxidant repertoire does not include catalase, an enzyme that decomposes H2O2 and is found in most aerobic organisms. In order to investigate the reason why T. cruzi does not have the catalase gene, a T. cruzi cell line which expresses this enzyme was generated. Parasites expressing catalase have an increased resistance to H2O2 in relation to wild type cells (WT). Moreover, pretreatment of parasites with a low concentration of H2O2 before treatment with higher concentrations makes the WT cells as resistant to H2O2 as cells expressing catalase. However, improvement in resistance to H2O2 after pretreatment was not observed with the same intensity in cells expressing catalase. Catalase expression in T. cruzi decreased the trypanothione reductase and increased superoxide dismutase levels, which resulted in higher levels of H2O2 after H2O2 treatment. More important, although the heterologous expression of catalase contributed to higher proliferation rates in the insect vector, expression of catalase does not induce a large increase in virulence of mice. These results, associated with the facts that catalase is present in monoxenous trypanosomatids and that H2O2 can act as second messenger, indicate that the absence of the catalase gene in T. cruzi was important in order to allow cells with a better capacity in sensing oxidative stress