Inhibition of Trypanosoma cruzi proline racemase affects host-parasite interactions and the outcome of in vitro infection.
Proline racemase is an important enzyme of Trypanosoma cruzi and has been shown to be an effective mitogen for B cells, thus contributing to the parasite's immune evasion and persistence in the human host. Recombinant epimastigote parasites overexpressing TcPRAC genes coding for proline racemase present an augmented ability to differentiate into metacyclic infective forms and subsequently penetrate host-cells in vitro. Here we demonstrate that both anti T. cruzi proline racemase antibodies and the specific proline racemase inhibitor pyrrole-2-carboxylic acid significantly affect parasite infection of Vero cells in vitro. This inhibitor also hampers T. cruzi intracellular differentiation.
Coutinho
Leticia
L
Laboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz-Fiocruz, Av Brasil 4365, 21045-900 Rio de Janeiro, RJ, Brasil.
Ferreira
Marcelo Alves
MA
Cosson
Alain
A
Batista
Marcos Meuser
MM
Batista
Denise da Gama Jaén
Dda G
Minoprio
Paola
P
Degrave
Wim M
WM
Berneman
Armand
A
Soeiro
Maria de Nazaré Correia
Mde N
D000591:Amino Acid Isomerases / Q000037:antagonists & inhibitors*; D000818:Animals; D002522:Chlorocebus aethiops; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006790:Host-Parasite Interactions / Q000502:physiology*; D008855:Microscopy, Electron, Scanning; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000502:physiology / Q000648:ultrastructure; D014709:Vero Cells
D004791:Enzyme Inhibitors; C002986:2-pyrrolecarboxylic acid; D011392:Proline; D000591:Amino Acid Isomerases; C022451:proline racemase