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主要易化超家族蛋白在转运体中的表达 - Δ 鉴定出一种药物转运体。

Expression of major facilitator superfamily protein in transporters - Δ identifies a drug transporter.

机构信息

Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110067, India.

Yeast Biofuel Group, International Centre for Genetic Engineering & Biotechnology, New Delhi, 110067, India.

出版信息

Future Microbiol. 2024;19(15):1293-1307. doi: 10.1080/17460913.2024.2389750. Epub 2024 Sep 5.

Abstract

To assess the functional relevance of a putative Major Facilitator Superfamily protein (PF3D7_0210300; 'MFSDT') as a drug transporter, using for orthologous protein expression. Complementary Determining Sequence encoding MFSDT was integrated into the genome of genetically engineered strain MSY8 via homologous recombination, followed by assessing its functional relevance as a drug transporter. The modified strain exhibited plasma membrane localization of MFSDT and characteristics of an Major Facilitator Superfamily transporter, conferring resistance to antifungals, ketoconazole and itraconazole. The nanomolar inhibitory effects of the drugs on the intra-erythrocytic growth of highlight their antimalarial properties. This study proposes MFSDT as a drug transporter, expanding the repertoire of the currently known antimalarial 'resistome'.

摘要

为了评估假定的主要易化超家族蛋白(PF3D7_0210300;'MFSDT')作为药物转运体的功能相关性,使用 进行同源蛋白表达。通过同源重组将编码 MFSDT 的互补决定序列整合到基因工程 菌株 MSY8 的基因组中,然后评估其作为药物转运体的功能相关性。修饰后的 菌株表现出 MFSDT 的质膜定位和主要易化超家族转运体的特征,对抗真菌药、酮康唑和伊曲康唑具有抗性。这些药物对 内的红细胞内生长的纳摩尔抑制作用突出了它们的抗疟特性。本研究提出 MFSDT 作为一种药物转运体,扩大了当前已知的抗疟“耐药组”的范围。

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