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

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-01-01 Epub Date: 2024-09-05 DOI:10.1080/17460913.2024.2389750

Preeti Maurya, Mohit Kumar, Ravi Jain, Haider Thaer Abdulhameed Almuqdadi, Harshita Singh, Aashima Gupta, Christoph Arenz, Naseem A Gaur, Shailja Singh

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Abstract

Aim: To assess the functional relevance of a putative Major Facilitator Superfamily protein (PF3D7_0210300; 'PfMFSDT') as a drug transporter, using Candida glabrata for orthologous protein expression.Methods: Complementary Determining Sequence encoding PfMFSDT was integrated into the genome of genetically engineered C. glabrata strain MSY8 via homologous recombination, followed by assessing its functional relevance as a drug transporter.Results & conclusion: The modified C. glabrata strain exhibited plasma membrane localization of PfMFSDT 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 Plasmodium falciparum highlight their antimalarial properties. This study proposes PfMFSDT as a drug transporter, expanding the repertoire of the currently known antimalarial 'resistome'.

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疟原虫主要促进剂超家族蛋白在转运体中的表达 - Δ念珠菌确定了一种药物转运体。

目的：评估假定的主要转运体超家族蛋白（PF3D7_0210300；"PfMFSDT"）作为药物转运体的功能相关性，并利用格氏念珠菌进行同源蛋白表达：方法：通过同源重组将编码 PfMFSDT 的互补确定序列整合到基因工程草履虫菌株 MSY8 的基因组中，然后评估其作为药物转运体的功能相关性：结果与结论：改造后的草履虫菌株表现出 PfMFSDT 的质膜定位和主要促进剂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。这些药物对恶性疟原虫红细胞内生长的纳摩尔抑制作用突出了它们的抗疟特性。这项研究认为 PfMFSDT 是一种药物转运体，扩大了目前已知的抗疟药物 "抗药性组 "的范围。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464