Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/46520
Title: Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their Association With Artemisinin Resistance
Authors: Faiza A. Siddiqui
Mynthia Cabrera
Meilian Wang
Awtum Brashear
Karen Kemirembe
Zenglei Wang
Jun Miao
Thanat Chookajorn
Zhaoqing Yang
Yaming Cao
Gang Dong
Philip J. Rosenthal
Liwang Cui
University of California, San Francisco
Kunming Medical University
Mahidol University
Medizinische Universitat Wien
China Medical University Shenyang
Pennsylvania State University
Keywords: Medicine
Issue Date: 2-Jul-2018
Citation: Journal of Infectious Diseases. Vol.218, No.3 (2018), 434-442
Abstract: © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. Background Falcipain-2a ([FP2a] PF3D7-1115700) is a Plasmodium falciparum cysteine protease and hemoglobinase. Functional FP2a is required for potent activity of artemisinin, and in vitro selection for artemisinin resistance selected for an FP2a nonsense mutation. Methods To investigate associations between FP2a polymorphisms and artemisinin resistance and to characterize the diversity of the enzyme in parasites from the China-Myanmar border, we sequenced the full-length FP2a gene in 140 P falciparum isolates collected during 2004-2011. Results The isolates were grouped into 8 different haplotype groups. Haplotype group I appeared in samples obtained after 2008, coinciding with implementation of artemisinin-based combination therapy in this region. In functional studies, compared with wild-type parasites, the FP2a haplotypes demonstrated increased ring survival, and all haplotype groups exhibited significantly reduced FP2a activity, with group I showing the slowest protease kinetics and reduced parasite fitness. Conclusions These results suggest that altered hemoglobin digestion due to FP2a mutations may contribute to artemisinin resistance.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85050817088&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/46520
ISSN: 15376613
00221899
Appears in Collections:Scopus 2018

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