Publication: Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their Association With Artemisinin Resistance
Submitted Date
Received Date
Accepted Date
Issued Date
2018-07-02
Copyright Date
Announcement No.
Application No.
Patent No.
Valid Date
Resource Type
Edition
Resource Version
Language
File Type
No. of Pages/File Size
ISBN
ISSN
15376613
00221899
00221899
eISSN
Scopus ID
WOS ID
Pubmed ID
arXiv ID
Call No.
Other identifier(s)
2-s2.0-85050817088
Journal Title
Volume
Issue
item.page.oaire.edition
Start Page
End Page
Access Rights
Access Status
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Physical Location
Bibliographic Citation
Journal of Infectious Diseases. Vol.218, No.3 (2018), 434-442
Citation
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 (2018). Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their Association With Artemisinin Resistance. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/46520.
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their Association With Artemisinin Resistance
Alternative Title(s)
Author's Affiliation
Author's E-mail
Editor(s)
Editor's Affiliation
Corresponding Author(s)
Creator(s)
Compiler
Advisor(s)
Illustrator(s)
Applicant(s)
Inventor(s)
Issuer
Assignee
Series
Has Part
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.