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© Research
Publication : Nature communications

Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature communications - 02 May 2018

Bopp S, Magistrado P, Wong W, Schaffner SF, Mukherjee A, Lim P, Dhorda M, Amaratunga C, Woodrow CJ, Ashley EA, White NJ, Dondorp AM, Fairhurst RM, Ariey F, Menard D, Wirth DF, Volkman SK

Link to Pubmed [PMID] – 29720620

Nat Commun 2018 May;9(1):1769

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.

https://www.ncbi.nlm.nih.gov/pubmed/29720620