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Expression of Plasmodium major facilitator superfamily protein in transporters - Δ Candida identifies a drug transporter.
- Source :
-
Future microbiology [Future Microbiol] 2024; Vol. 19 (15), pp. 1293-1307. Date of Electronic Publication: 2024 Sep 05. - Publication Year :
- 2024
-
Abstract
- Aim: To assess the functional relevance of a putative Major Facilitator Superfamily protein (PF3D7_0210300; ' Pf MFSDT') as a drug transporter, using Candida glabrata for orthologous protein expression. Methods: Complementary Determining Sequence encoding Pf MFSDT 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 Pf 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 Plasmodium falciparum highlight their antimalarial properties. This study proposes Pf MFSDT as a drug transporter, expanding the repertoire of the currently known antimalarial 'resistome'.
- Subjects :
- Protozoan Proteins genetics
Protozoan Proteins metabolism
Fungal Proteins genetics
Fungal Proteins metabolism
Itraconazole pharmacology
Ketoconazole pharmacology
Humans
Cell Membrane metabolism
Plasmodium falciparum genetics
Plasmodium falciparum drug effects
Plasmodium falciparum metabolism
Antifungal Agents pharmacology
Antifungal Agents metabolism
Membrane Transport Proteins genetics
Membrane Transport Proteins metabolism
Candida glabrata genetics
Candida glabrata metabolism
Candida glabrata drug effects
Antimalarials pharmacology
Antimalarials metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1746-0921
- Volume :
- 19
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Future microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 39235058
- Full Text :
- https://doi.org/10.1080/17460913.2024.2389750