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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/44990
Title: Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum
Authors: 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
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
Keywords: Biochemistry, Genetics and Molecular Biology;Chemistry;Physics and Astronomy
Issue Date: 1-Dec-2018
Citation: Nature Communications. Vol.9, No.1 (2018)
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.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85046402237&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/44990
ISSN: 20411723
Appears in Collections:Scopus 2018

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