ArticleMalaria journal2015
PfMDR2 and PfMDR5 are dispensable for Plasmodium falciparum asexual parasite multiplication but change in vitro susceptibility to anti-malarial drugs.
Article in Malaria journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 18 citations in OpenAlex.
- Updated List of Transport Proteins inFrontiers in cellular and infection microbiology · 2022Review
- Article
- Absence of Association between Methylene Blue Reduced Susceptibility and Polymorphisms in 12 Genes Involved in Antimalarial Drug Resistance in AfricanPharmaceuticals (Basel, Switzerland) · 2021Article
- 3-Hydroxy-propanamidines, a New Class of Orally Active Antimalarials Targeting Plasmodium falciparum.Journal of medicinal chemistry · 2021Article
- Antitumor Research on Artemisinin and Its Bioactive Derivatives.Natural products and bioprospecting · 2018Review
- Association between Polymorphisms in the PfAntimicrobial agents and chemotherapy · 2017Article
- SC83288 is a clinical development candidate for the treatment of severe malaria.Nature communications · 2017Article
- Artemisinin-based antimalarial research: application of biotechnology to the production of artemisinin, its mode of action, and the mechanism of resistance of Plasmodium parasites.Journal of natural medicines · 2016Review
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5 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundMembrane-associated ATP binding cassette (ABC) transport proteins hydrolyze ATP in order to translocate a broad spectrum of substrates, from single ions to macromolecules across membranes. In humans, members from this transport family have been linked to drug resistance phenotypes, e.g., tumour resistance by enhanced export of chemotherapeutic agents from cancer cells due to gene amplifications or polymorphisms in multidrug resistance (MDR) protein 1. Similar mechanisms have linked the Plasmodium falciparum PfMDR1 transporter to anti-malarial drug resistance acquisition. In this study, the possible involvement of two related MDR proteins, PfMDR2 and PfMDR5, to emerging drug resistance is investigated by a reverse genetics approach.
methodsA homologous double crossover strategy was used to generate P. falciparum parasites lacking the Pfmdr2 (PfΔmdr2) or Pfmdr5 (PfΔmdr5) gene. Plasmodium lactate dehydrogenase activity was used as read-out for sensitivity to artemisinin (ART), atovaquone (ATO), dihydroartemisinin (DHA), chloroquine (CQ), lumefantrine (LUM), mefloquine (MQ), and quinine (QN). Differences in half maximal inhibitory concentration (IC₅₀) values between wild type and each mutant line were determined using a paired t-test.
resultsBoth PfΔmdr2 and PfΔmdr5 clones were capable of asexual multiplication. Upon drug exposure, PfΔmdr2 showed a marginally decreased sensitivity to ATO (IC₅₀ of 1.2 nM to 1.8 nM), MQ (124 nM to 185 nM) and QN (40 nM to 70 nM), as compared to wild type (NF54) parasites. On the other hand, PfΔmdr5 showed slightly increased sensitivity to ART (IC₅₀ of 26 nM to 19 nM).
conclusionBoth Pfmdr2 and Pfmdr5 are dispensable for blood stage development while the deletion lines show altered sensitivity profiles to commonly used anti-malarial drugs. The findings show for the first time that next to PfMDR2, the PfMDR5 transport protein could play a role in emerging drug resistance.
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