PfCRT mutations conferring piperaquine resistance in falciparum malaria shape the kinetics of quinoline drug binding and transport
The chloroquine resistance transporter (PfCRT) confers resistance to a wide range of quinoline and quinoline-like antimalarial drugs in Plasmodium falciparum, with local drug histories driving its evolution and, hence, the drug transport specificities. For example, the change in prescription practic...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
June 7, 2023
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| In: |
PLoS pathogens
Year: 2023, Volume: 19, Issue: 6, Pages: 1-35 |
| ISSN: | 1553-7374 |
| DOI: | 10.1371/journal.ppat.1011436 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1371/journal.ppat.1011436 Verlag, kostenfrei, Volltext: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011436 
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| Author Notes: | Guillermo M. Gomez, Giulia D’Arrigo, Cecilia P. Sanchez, Fiona Berger, Rebecca C. Wade, Michael Lanzer |
| Summary: | The chloroquine resistance transporter (PfCRT) confers resistance to a wide range of quinoline and quinoline-like antimalarial drugs in Plasmodium falciparum, with local drug histories driving its evolution and, hence, the drug transport specificities. For example, the change in prescription practice from chloroquine (CQ) to piperaquine (PPQ) in Southeast Asia has resulted in PfCRT variants that carry an additional mutation, leading to PPQ resistance and, concomitantly, to CQ re-sensitization. How this additional amino acid substitution guides such opposing changes in drug susceptibility is largely unclear. Here, we show by detailed kinetic analyses that both the CQ- and the PPQ-resistance conferring PfCRT variants can bind and transport both drugs. ... |
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| Item Description: | Gesehen am 07.12.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1553-7374 |
| DOI: | 10.1371/journal.ppat.1011436 |