Publication: Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum
Issued Date
2018-12-01
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20411723
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2-s2.0-85046402237
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Mahidol University
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SCOPUS
Bibliographic Citation
Nature Communications. Vol.9, No.1 (2018)
Suggested Citation
Selina Bopp, Pamela Magistrado, Wesley Wong, Stephen F. Schaffner, Angana Mukherjee, Pharath Lim, Mehul Dhorda, Chanaki Amaratunga, Charles J. Woodrow, Elizabeth A. Ashley, Nicholas J. White, Arjen M. Dondorp, Rick M. Fairhurst, Frederic Ariey, Didier Menard, Dyann F. Wirth, Sarah K. Volkman Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum. Nature Communications. Vol.9, No.1 (2018). doi:10.1038/s41467-018-04104-z Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/44990
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Title
Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum
Other Contributor(s)
Harvard School of Public Health
Universite Paris Descartes
University of Oxford
Mahidol University
CNRS Centre National de la Recherche Scientifique
National Institutes of Health, Bethesda
Simmons College
Institut Pasteur, Paris
Broad Institute
Inserm
Myanmar Oxford Clinical Research Unit
Worldwide Antimalarial Resistance Network
Universite Paris Descartes
University of Oxford
Mahidol University
CNRS Centre National de la Recherche Scientifique
National Institutes of Health, Bethesda
Simmons College
Institut Pasteur, Paris
Broad Institute
Inserm
Myanmar Oxford Clinical Research Unit
Worldwide Antimalarial Resistance Network
Abstract
© 2018 The Author(s). Multidrug resistant Plasmodium falciparum in Southeast Asia endangers regional malaria elimination and threatens to spread to other malaria endemic areas. Understanding mechanisms of piperaquine (PPQ) resistance is crucial for tracking its emergence and spread, and to develop effective strategies for overcoming it. Here we analyze a mechanism of PPQ resistance in Cambodian parasites. Isolates exhibit a bimodal dose-response curve when exposed to PPQ, with the area under the curve quantifying their survival in vitro. Increased copy number for plasmepsin II and plasmepsin III appears to explain enhanced survival when exposed to PPQ in most, but not all cases. A panel of isogenic subclones reinforces the importance of plasmepsin II-III copy number to enhanced PPQ survival. We conjecture that factors producing increased parasite survival under PPQ exposure in vitro may drive clinical PPQ failures in the field.