Inhibition of Trypanosoma cruzi proline racemase affects host-parasite interactions and the outcome of in vitro infection

Mem Inst Oswaldo Cruz. 2009 Dec;104(8):1055-62. doi: 10.1590/s0074-02762009000800001.

Abstract

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.

MeSH terms

  • Amino Acid Isomerases / antagonists & inhibitors*
  • Animals
  • Chlorocebus aethiops
  • Enzyme Inhibitors / pharmacology*
  • Host-Parasite Interactions / physiology*
  • Microscopy, Electron, Scanning
  • Proline / analogs & derivatives*
  • Proline / pharmacology
  • Trypanosoma cruzi / enzymology*
  • Trypanosoma cruzi / physiology
  • Trypanosoma cruzi / ultrastructure
  • Vero Cells

Substances

  • Enzyme Inhibitors
  • 2-pyrrolecarboxylic acid
  • Proline
  • Amino Acid Isomerases
  • proline racemase