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

0538237 - BC 2021 RIV GB eng J - Journal Article
Horáková, Eva - Faktorová, Drahomíra - Kraeva, N. - Kaur, Binnypreet - Van den Abbeele, J. - Yurchenko, V. - Lukeš, Julius
Catalase compromises the development of the insect and mammalian stages of Trypanosoma brucei.
FEBS Journal. Roč. 287, č. 5 (2020), s. 964-977. ISSN 1742-464X. E-ISSN 1742-4658
R&D Projects: GA MŠMT(CZ) LL1601; GA MŠMT(CZ) EF16_019/0000759
EU Projects: European Commission(BE) COST Action CA15133
Institutional support: RVO:60077344
Keywords : superoxide-dismutase * plasmodium-falciparum * metabolism * mitochondria * biogenesis * mechanisms * expression * diversity * evolution * pathogen * catalase * development * hydrogen peroxide * trypanosoma
OECD category: Genetics and heredity (medical genetics to be 3)
Impact factor: 5.542, year: 2020
Method of publishing: Limited access
https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/febs.15083

Catalase is a widespread heme-containing enzyme, which converts hydrogen peroxide (H2O2) to water and molecular oxygen, thereby protecting cells from the toxic effects of H2O2. Trypanosoma brucei is an aerobic protist, which conspicuously lacks this potent enzyme, present in virtually all organisms exposed to oxidative stress. To uncover the reasons for its absence in T. brucei, we overexpressed different catalases in procyclic and bloodstream stages of the parasite. The heterologous enzymes originated from the related insect-confined trypanosomatid Crithidia fasciculata and the human. While the trypanosomatid enzyme (cCAT) operates at low temperatures, its human homolog (hCAT) is adapted to the warm-blooded environment. Despite the presence of peroxisomal targeting signal in hCAT, both human and C. fasciculata catalases localized to the cytosol of T. brucei. Even though cCAT was efficiently expressed in both life cycle stages, the enzyme was active in the procyclic stage, increasing cell's resistance to the H2O2 stress, yet its activity was suppressed in the cultured bloodstream stage. Surprisingly, following the expression of hCAT, the ability to establish the T. brucei infection in the tsetse fly midgut was compromised. In the mouse model, hCAT attenuated parasitemia and, consequently, increased the host's survival. Hence, we suggest that the activity of catalase in T. brucei is beneficial in vitro, yet it becomes detrimental for parasite's proliferation in both invertebrate and vertebrate hosts, leading to an inability to carry this, otherwise omnipresent, enzyme.
Permanent Link: http://hdl.handle.net/11104/0316063