Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their Association With Artemisinin Resistance
© 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. Functi...
Saved in:
Main Authors: | , , , , , , , , , , , , |
---|---|
Other Authors: | |
Format: | Article |
Published: |
2019
|
Subjects: | |
Online Access: | https://repository.li.mahidol.ac.th/handle/123456789/46520 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Mahidol University |
id |
th-mahidol.46520 |
---|---|
record_format |
dspace |
spelling |
th-mahidol.465202019-08-28T13:00:32Z Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their Association With Artemisinin Resistance 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 Medicine © 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. 2019-08-28T06:00:32Z 2019-08-28T06:00:32Z 2018-07-02 Article Journal of Infectious Diseases. Vol.218, No.3 (2018), 434-442 10.1093/infdis/jiy188 15376613 00221899 2-s2.0-85050817088 https://repository.li.mahidol.ac.th/handle/123456789/46520 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85050817088&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 |
Medicine |
spellingShingle |
Medicine 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 Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their Association With Artemisinin Resistance |
description |
© 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. |
author2 |
University of California, San Francisco |
author_facet |
University of California, San Francisco 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 |
format |
Article |
author |
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 |
author_sort |
Faiza A. Siddiqui |
title |
Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their Association With Artemisinin Resistance |
title_short |
Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their Association With Artemisinin Resistance |
title_full |
Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their Association With Artemisinin Resistance |
title_fullStr |
Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their Association With Artemisinin Resistance |
title_full_unstemmed |
Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their Association With Artemisinin Resistance |
title_sort |
plasmodium falciparum falcipain-2a polymorphisms in southeast asia and their association with artemisinin resistance |
publishDate |
2019 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/46520 |
_version_ |
1763494372647632896 |