Expression of Plasmodium Major Facilitator Superfamily Protein in Transporters-Delta Candida Identifies a Drug Transporter

Aim: To assess the functional relevance of a putative Major Facilitator Superfamily (MFS) protein (PF3D7_0210300; PfMFS_DT) as a drug transporter, using Candida glabrata for orthologous protein expression. Methods: CDS encoding PfMFS_DT 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 and Conclusion: The modified C. glabrata strain exhibited plasma membrane localization of PfMFS_DT and characteristics of an MFS transporter, conferring resistance to antifungals, ketoconazole and itraconazole. The nanomolar inhibitory effects of the drugs on the intra-erythrocytic growth of P. falciparum highlight their antimalarial properties. This study proposes PfMFS_DT as a drug transporter, expanding the repertoire of the currently known antimalarial resistome.