New Insights into the Role of the Trypanosoma cruzi Aldo-Keto Reductase TcAKR

Chagas disease is a zoonotic infectious disease caused by the protozoan parasite Trypanosoma cruzi. It is distributed worldwide, affecting around 7 million people; there is no effective treatment, and it constitutes a leading cause of disability and premature death in the Americas. Only two drugs ar...

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Bibliographic Details
Published in:Pathogens (Basel) 2023-01, Vol.12 (1), p.85
Main Authors: Díaz-Viraqué, Florencia, Chiribao, María Laura, Paes-Vieira, Lisvane, Machado, Matias R, Faral-Tello, Paula, Tomasina, Ramiro, Trochine, Andrea, Robello, Carlos
Format: Article
Language:English
Subjects:
Aldo-keto reductase
aldo-keto reductases
Antibodies
antipodal sites
Benznidazole
Cell cycle
Chagas disease
death
Drug metabolism
Enzymes
Epimastigotes
Infectious diseases
kinetoplast
Life cycles
Mitochondria
mitochondrial enzyme
Nifurtimox
nitro compounds
Parasites
people
pharmacokinetics
Phylogenetics
Plasmids
prostaglandin F2α synthase
Proteins
Protozoa
Reductases
Structural analysis
trypanocides
Trypanosoma cruzi
Vector-borne diseases
Zoonoses
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Summary:Chagas disease is a zoonotic infectious disease caused by the protozoan parasite Trypanosoma cruzi. It is distributed worldwide, affecting around 7 million people; there is no effective treatment, and it constitutes a leading cause of disability and premature death in the Americas. Only two drugs are currently approved for the treatment, Benznidazole and Nifurtimox, and both have to be activated by reducing the nitro-group. The T. cruzi aldo-keto reductase (TcAKR) has been related to the metabolism of benznidazole. TcAKR has been extensively studied, being most efforts focused on characterizing its implication in trypanocidal drug metabolism; however, little is known regarding its biological role. Here, we found that TcAKR is confined, throughout the entire life cycle, into the parasite mitochondria providing new insights into its biological function. In particular, in epimastigotes, TcAKR is associated with the kinetoplast, which suggests additional roles of the protein. The upregulation of TcAKR, which does not affect TcOYE expression, was correlated with an increase in PGF2α, suggesting that this enzyme is related to PGF2α synthesis in T. cruzi. Structural analysis showed that TcAKR contains a catalytic tetrad conserved in the AKR superfamily. Finally, we found that TcAKR is also involved in Nfx metabolization.
ISSN:2076-0817
2076-0817
DOI:10.3390/pathogens12010085