Peroxiredoxins from Trypanosoma cruzi: virulence factors and drug targets for treatment of Chagas disease?
Cytosolic and mitochondrial Trypanosoma cruzi tryparedoxin peroxidases belong to the family of 2-Cys peroxiredoxins. These enzymes play an essential role as antioxidants by their peroxidase and peroxynitrite reductase activities. TXNPx are key components of the trypanosomatid peroxide detoxification pathways. The aim of this work was to determine the role of TXNPx as virulence factors in the parasite, and whether these enzymes are good candidates for drug design. We observed that peroxiredoxins are not highly abundant proteins expressed at similar levels throughout the T. cruzi life cycle. In order to study the role of c-TXNPx and m-TXNPx in invasion and infectivity, parasites overexpressing TXNPx were produced, and infection experiments were carried out using phagocytic and non-phagocytic cells. Parasites overexpressing peroxiredoxins showed a significant increase in infectivity with respect to the control ones. The results presented in this work point out that the T. cruzi peroxiredoxins are important in survival, replication and differentiation of T. cruzi and could constitute virulence factors. Moreover, their expression in the infective forms of the life cycle and their low intracellular concentration make them good candidates to become targets for drug design.
Piñeyro
María Dolores
MD
Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Gral Flores 2125, 11800, Montevideo, Uruguay.
Parodi-Talice
Adriana
A
Arcari
Talia
T
Robello
Carlos
C
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000517:prevention & control; D008264:Macrophages / Q000378:metabolism; D054464:Peroxiredoxins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010587:Phagocytosis; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity*; D037521:Virulence Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*
D037521:Virulence Factors; D054464:Peroxiredoxins