Catalase expression impairs oxidative stress-mediated signalling inTrypanosoma cruzi

Abstract

SUMMARYTrypanosoma cruzi is exposed to oxidative stresses during its life cycle, and amongst the strategies employed by this parasite to deal with these situations sits a peculiar trypanothione-dependent antioxidant system. Remarkably, T. cruzi’s antioxidant repertoire does not include catalase. In an attempt to shed light on what are the reasons by which this parasite lacks this enzyme, a T. cruzi cell line stably expressing catalase showed an increased resistance to hydrogen peroxide (H2O2) when compared with wild-type cells. Interestingly, preconditioning carried out with low concentrations of H2O2 led untransfected parasites to be as much resistant to this oxidant as cells expressing catalase, but did not induce the same level of increased resistance in the latter ones. Also, presence of catalase decreased trypanothione reductase and increased superoxide dismutase levels in T. cruzi, resulting in higher levels of residual H2O2 after challenge with this oxidant. Although expression of catalase contributed to elevated proliferation rates of T. cruzi in Rhodnius prolixus, it failed to induce a significant increase of parasite virulence in mice. Altogether, these results indicate that the absence of a gene encoding catalase in T. cruzi has played an important role in allowing this parasite to develop a shrill capacity to sense and overcome oxidative stress.

Catalase compromises the development of the insect and mammalian stages of Trypanosoma brucei

“…It has been shown that after 2 days of heme starvation, only 6% of the catalase activity in C. fasciculata was retained, whereas the oxygen consumption and cytochrome‐mediated respiration remained unaffected . In T. brucei , we recapitulated (to some extent) the phenotype observed in T. cruzi after the expression of a bacterial catalase in vitro . However, the in vivo phenotype was dramatically different.…”

“…The presence of the bacterial catalase also affected the fitness of T. cruzi in vivo , with elevated proliferation rate of the promastigotes in the insect vector Rhodnius prolixus , but no significant influence on parasite virulence in the vertebrate host. Overall, this study documented a marginally positive impact of a heterologous catalase expression on parasite’s fitness .…”

“…Moreover, the expression of catalase contributed to the elevated proliferation of T. cruzi in the insect vector but did not significantly increase parasite virulence in the mammalian host . In T. brucei , we demonstrated that the induced expression of catalase significantly affected the ability of the insect‐dwelling PCF to establish infection and multiply in the tsetse fly midgut.…”

“…Overall, this study documented a marginally positive impact of a heterologous catalase expression on parasite's fitness [31]. This study aimed to investigate the impact of catalase expression in an extracellular parasite T. brucei.…”

“…A crucial role of H 2 O 2 in differentiation and virulence has been demonstrated for another trypanosomatid, Trypanosoma cruzi , the intracellular parasite causing Chagas disease . Importantly, when catalase from Escherichia coli was heterologously expressed in T. cruzi , the ability of the parasite to signal oxidative stress was altered . Levels of the T. cruzi antioxidant enzymes, such as trypanothione reductase and superoxide dismutase, were decreased and increased, respectively.…”