Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum
© 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 e...
Saved in:
Main Authors: | , , , , , , , , , , , , , , , , |
---|---|
Other Authors: | |
Format: | Article |
Published: |
2019
|
Subjects: | |
Online Access: | https://repository.li.mahidol.ac.th/handle/123456789/44990 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Mahidol University |
id |
th-mahidol.44990 |
---|---|
record_format |
dspace |
spelling |
th-mahidol.449902019-08-28T13:56:44Z Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum 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 Biochemistry, Genetics and Molecular Biology Chemistry Physics and Astronomy © 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. 2019-08-23T10:25:28Z 2019-08-23T10:25:28Z 2018-12-01 Article Nature Communications. Vol.9, No.1 (2018) 10.1038/s41467-018-04104-z 20411723 2-s2.0-85046402237 https://repository.li.mahidol.ac.th/handle/123456789/44990 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85046402237&origin=inward |
institution |
Mahidol University |
building |
Mahidol University Library |
continent |
Asia |
country |
Thailand Thailand |
content_provider |
Mahidol University Library |
collection |
Mahidol University Institutional Repository |
topic |
Biochemistry, Genetics and Molecular Biology Chemistry Physics and Astronomy |
spellingShingle |
Biochemistry, Genetics and Molecular Biology Chemistry Physics and Astronomy 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 |
description |
© 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. |
author2 |
Harvard School of Public Health |
author_facet |
Harvard School of Public Health 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 |
format |
Article |
author |
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 |
author_sort |
Selina Bopp |
title |
Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum |
title_short |
Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum |
title_full |
Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum |
title_fullStr |
Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum |
title_full_unstemmed |
Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum |
title_sort |
plasmepsin ii-iii copy number accounts for bimodal piperaquine resistance among cambodian plasmodium falciparum |
publishDate |
2019 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/44990 |
_version_ |
1763495909584273408 |