title: MRP1 mediates folate transport and antifolate sensitivity in Plasmodium falciparum.
abstract: Multidrug resistance-associated proteins (MRP) of Plasmodium falciparum have been associated with altered drug sensitivity. Knowledge on MRP substrate specificity is indispensible for the characterization of resistance mechanisms and identifying its physiological roles. An untargeted metabolomics approach detected decreased folate concentrations in red blood cells infected with schizont stage parasites lacking expression of MRP1. Furthermore, a tenfold decrease in sensitivity toward the folate analog methotrexate was detected for parasites lacking MRP1. PfMRP1 is involved in the export of folate from parasites into red blood cells and is therefore a relevant factor for efficient malaria treatment through the folate pathway.
authors.affiliation: Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Sanna R
authors.initials: SR
authors.lastname: Rijpma
authors.affiliation: Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: van der Velden
authors.affiliation: Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Bilos
authors.affiliation: Division of Molecular Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Jansen
authors.affiliation: Division of Molecular Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Sunny
authors.initials: S
authors.lastname: Mahakena
authors.affiliation: Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Frans G M
authors.initials: FG
authors.lastname: Russel
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.affiliation: Division of Molecular Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: van de Wetering
authors.affiliation: Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jan B
authors.initials: JB
authors.lastname: Koenderink
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D001692:Biological Transport; D018432:Drug Resistance, Multiple; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D005492:Folic Acid / Q000378:metabolism*; D005493:Folic Acid Antagonists / Q000737:chemistry / Q000494:pharmacology*; D055786:Gene Knockout Techniques; D006801:Humans; D055432:Metabolomics; D008727:Methotrexate / Q000737:chemistry / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D000962:Antimalarials; D005492:Folic Acid; D005493:Folic Acid Antagonists; D008727:Methotrexate; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins
keywords: ABC transporter; Plasmodium falciparum; folate; multidrug resistance protein; multidrug resistance-associated proteins