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抑制克氏锥虫脯氨酰外消旋酶影响宿主-寄生虫相互作用和体外感染的结果。

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

机构信息

Laboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz-Fiocruz, Av Brasil 4365, 21045-900 Rio de Janeiro, RJ, Brasil.

出版信息

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.

摘要

脯氨酸外消旋酶是克氏锥虫的一种重要酶,已被证明可有效刺激 B 细胞增殖,从而有助于寄生虫逃避宿主的免疫反应并在宿主体内存续。过表达编码脯氨酸外消旋酶的 TcPRAC 基因的重组体外培养的锥虫可增强分化为循环感染性形态的能力,并随后在体外穿透宿主细胞。在这里,我们证明了抗 T. cruzi 脯氨酸外消旋酶抗体和脯氨酸外消旋酶抑制剂吡咯-2-羧酸均可显著影响体外 Vero 细胞的寄生虫感染。该抑制剂还会阻碍 T. cruzi 的细胞内分化。

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