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MRP 1 mediates folate transport and antifolate sensitivity in Plasmodium falciparum
Author(s) -
Rijpma Sanna R.,
Velden Maarten,
Bilos Albert,
Jansen Robert S.,
Mahakena Sunny,
Russel Frans G. M.,
Sauerwein Robert W.,
Wetering Koen,
Koenderink Jan B.
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12079
Subject(s) - plasmodium falciparum , antifolate , multidrug resistance associated proteins , methotrexate , biochemistry , folic acid , malaria , drug resistance , multiple drug resistance , chemistry , biology , pharmacology , microbiology and biotechnology , immunology , medicine , transporter , atp binding cassette transporter , antimetabolite , gene
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 MRP 1. Furthermore, a tenfold decrease in sensitivity toward the folate analog methotrexate was detected for parasites lacking MRP 1. Pf MRP 1 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.