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Texto completo SciELO Brasil
Texto completo
Id: lil-538164
Autor: Coutinho, Leticia; Ferreira, Marcelo Alves; Cosson, Alain; Batista, Marcos Meuser; Batista, Denise da Gama Jaén; Minoprio, Paola; Degrave, Wim M; Berneman, Armand; Soeiro, Maria de Nazaré Correia.
Título: Inhibition of Trypanosoma cruzi proline racemase affects host-parasite interactions and the outcome of in vitro infection
Fonte: Mem. Inst. Oswaldo Cruz;104(8):1055-1062, Dec. 2009. ilus.
Idioma: en.
Resumo: 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.
Descritores: Isomerases de Aminoácido/antagonistas & inibidores
Inibidores Enzimáticos/farmacologia
Interações Hospedeiro-Parasita/fisiologia
Prolina/análogos & derivados
Trypanosoma cruzi/enzimologia
-Chlorocebus aethiops
Microscopia Eletrônica de Varredura
Trypanosoma cruzi/fisiologia
Trypanosoma cruzi/ultraestrutura
Células Vero
Limites: Animais
Responsável: BR1.1 - BIREME

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Texto completo SciELO Brasil
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Id: lil-520892
Autor: Coatnoan, Nicolas; Berneman, Armand; Chamond, Nathalie; Minoprio, Paola.
Título: Proline racemases: insights into Trypanosoma cruzi peptides containing D-proline
Fonte: Mem. Inst. Oswaldo Cruz;104(supl.1):295-300, July 2009. ilus, tab, graf.
Idioma: en.
Resumo: Trypanosoma cruzi proline racemases (TcPRAC) are homodimeric enzymes that interconvert the L and D-enantiomers of proline. At least two paralogous copies of proline racemase (PR) genes are present per parasite haploid genome and they are differentially expressed during T. cruzi development. Non-infective epimastigote forms that overexpress PR genes differentiate more readily into metacyclic infective forms that are more invasive to host cells, indicating that PR participates in mechanisms of virulence acquisition. Using a combination of biochemical and enzymatic methods, we show here that, in addition to free D-amino acids, non-infective epimastigote and infective metacyclic parasite extracts possess peptides composed notably of D-proline. The relative contribution of TcPRAC to D-proline availability and its further assembly into peptides was estimated through the use of wild-type parasites and parasites over-expressing TcPRAC genes. Our data suggest that D-proline-bearing peptides, similarly to the mucopeptide layer of bacterial cell walls, may be of benefit to T. cruzi by providing resistance against host proteolytic mechanisms.
Descritores: Isomerases de Aminoácido/genética
Proteínas de Protozoários/química
Trypanosoma cruzi/química
-Isomerases de Aminoácido/metabolismo
Regulação da Expressão Gênica
Proteínas de Protozoários/genética
Proteínas de Protozoários/metabolismo
Trypanosoma cruzi/genética
Trypanosoma cruzi/metabolismo
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME

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