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Status |
Public on Jan 31, 2022 |
Title |
The Plasmodium falciparum protein PfMRP1 functions as an influx ABC transporter |
Organisms |
Plasmodium falciparum 3D7; Plasmodium falciparum Dd2 |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Adenosine triphosphate (ATP)-binding cassette (ABC) transporters play an important role in mediating solute or drug transport across cellular membranes. Although this class of transporters has been well characterized in diverse organisms little is known about the physiological roles in Plasmodium falciparum, the deadliest malaria parasite species. We studied the Plasmodium falciparum Multidrug Resistance-associated Protein 1 (PfMRP1; PF3D7_0112200), an ABC transporter localized to the parasite plasma membrane, generating genetic disrupted parasites. We demonstrate that parasites with disrupted pfmrp1 are resistant to folate analogs, methotrexate and aminopterin, with antimalarial activity. This phenotype occurs due to reduction in compound accumulation in the parasite cytoplasm. Phylogenetic analysis supports pfmrp1 being distantly related to ABC transporters in other eukaryotes, suggesting an unusual function. We propose that PfMRP1 can act as a solute importer, a function not previously observed in this organism.
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Overall design |
Study focused on the impact of truncating the PfMRP1 transporter on P. falciparum physiology and drug response. RNA was extrated after tighly synchronization of parasites of estimatly 28-32h after cycle initiation. One sample was colected for wild-type and knock-out for the two strains in study the 3D7 and Dd2.
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Contributor(s) |
Silva M, Calçada C, Osório NS, Baptista V, Thathy V, Teixeira M, Reid AJ, Ferreira PF, Fidock DA, Veiga MI |
Citation missing |
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Submission date |
Jan 28, 2022 |
Last update date |
Jan 31, 2022 |
Contact name |
Nuno S. Osório |
E-mail(s) |
nosorio@med.uminho.pt
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Organization name |
ICVS
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Street address |
Campus de Gualtar
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City |
Braga |
ZIP/Postal code |
4710-057 |
Country |
Portugal |
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Platforms (2) |
GPL24926 |
Illumina HiSeq 2500 (Plasmodium falciparum 3D7) |
GPL31288 |
Illumina HiSeq 2500 (Plasmodium falciparum Dd2) |
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Samples (4)
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Relations |
BioProject |
PRJNA801625 |