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Published on: July 31, 2019
Catalase expression impairs oxidative stress-mediated signalling in Trypanosoma cruzi
Anna Cláudia Guimarães Freire1, Ceres Luciana Alves1, Grazielle Ribeiro Goes1
1Departamento de Bioquímica e Imunologia,Universidade Federal de Minas Gerais,Belo Horizonte, MG,Brazil.
Abstract:
Trypanosoma 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.
Insights
Trypanosoma cruzi lacks catalase, an enzyme crucial for managing oxidative stress. Introducing catalase enhanced parasite resistance to hydrogen peroxide but revealed a sophisticated stress-sensing mechanism in its absence.
Area of Science:
- Parasitology
- Molecular Biology
- Biochemistry
Background:
- Trypanosoma cruzi faces oxidative stress during its life cycle.
- The parasite utilizes a unique trypanothione-dependent antioxidant system.
- Notably, T. cruzi lacks the enzyme catalase, prompting investigation into this absence.
Purpose of the Study:
- To investigate the functional role of catalase in Trypanosoma cruzi.
- To understand the implications of catalase absence on parasite's oxidative stress response.
- To explore the impact of catalase expression on T. cruzi proliferation and virulence.
Main Methods:
- Generation of a T. cruzi cell line stably expressing catalase.
- Comparison of hydrogen peroxide resistance between transfected and wild-type cells.
- Analysis of antioxidant enzyme levels (trypanothione reductase, superoxide dismutase) and parasite proliferation/virulence.
Main Results:
- Catalase expression in T. cruzi increased resistance to hydrogen peroxide.
- Preconditioning with low hydrogen peroxide levels enhanced resistance in wild-type but not catalase-expressing cells.
- Catalase presence altered levels of other antioxidant enzymes and H2O2, impacting proliferation but not virulence in mice.
Conclusions:
- The absence of catalase in T. cruzi is linked to its heightened ability to sense and manage oxidative stress.
- Catalase expression influences the parasite's antioxidant system and proliferation capacity.
- The lack of catalase may be a key factor in the evolutionary adaptation of T. cruzi's stress response.
