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Sulfadiazine resistance in Toxoplasma gondii: no involvement of overexpression or polymorphisms in genes of therapeutic targets and ABC transporters

机译:弓形虫对磺胺嘧啶的抗药性:治疗靶标和ABC转运蛋白的基因中不涉及过表达或多态性

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Several treatment failures have been reported for the treatment of toxoplasmic encephalitis, chorioretinitis, and congenital toxoplasmosis. Recently we found three Toxoplasma gondii strains naturally resistant to sulfadiazine and we developed in vitro two sulfadiazine resistant strains, RH-RSDZ and ME-49-RSDZ, by gradual pressure. In Plasmodium, common mechanisms of drug resistance involve, among others, mutations and/or amplification within genes encoding the therapeutic targets dhps and dhfr and/or the ABC transporter genes family. To identify genotypic and/or phenotypic markers of resistance in T. gondii, we sequenced and analyzed the expression levels of therapeutic targets dhps and dhfr, three ABC genes, two Pgp, TgABC.B1 and TgABC.B2, and one MRP, TgABC.C1, on sensitive strains compared to sulfadiazine resistant strains. Neither polymorphism nor overexpression was identified. Contrary to Plasmodium, in which mutations and/or overexpression within gene targets and ABC transporters are involved in antimalarial resistance, T. gondii sulfadiazine resistance is not related to these toxoplasmic genes studied.
机译:据报道,弓形体脑炎,脉络膜视网膜炎和先天性弓形体病的治疗失败。最近,我们发现了三株对磺胺嘧啶具有天然抗性的弓形虫,我们通过渐进压力在体外开发了两种磺胺嘧啶抗性菌株RH-RSDZ和ME-49-RSDZ。在疟原虫中,耐药性的常见机制尤其涉及编码治疗靶标dhps和dhfr和/或ABC转运蛋白基因家族的基因内的突变和/或扩增。为了鉴定弓形虫抗性的基因型和/或表型标记,我们测序并分析了治疗靶点dhps和dhfr,三个ABC基因,两个Pgp,TgABC.B1和TgABC.B2以及一个MRP,TgABC的表达水平。 C1,与耐磺胺嘧啶的菌株相比敏感菌株。既没有发现多态性也没有发现过表达。与疟原虫相反,在疟原虫中,基因靶标中的突变和/或过表达和ABC转运蛋白参与了抗疟药的耐药性,刚地弓形虫磺胺嘧啶的耐药性与这些研究的弓形虫基因无关。

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