Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance
Artemisinin resistance in Plasmodium falciparum threatens global efforts to control and eliminate malaria. Polymorphisms in the kelch domain–carrying protein K13 are associated with artemisinin resistance, but the underlying molecular mechanisms are unknown. We analyzed the in vivo transcriptomes of...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2016
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| Online Access: | https://hdl.handle.net/10356/83802 http://hdl.handle.net/10220/41453 |
| _version_ | 1824453186511962112 |
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| author | Mok, S. Ashley, E. A. Ferreira, P. E. Zhu, L. Lin, Z. Yeo, T. Chotivanich, K. Imwong, M. Pukrittayakamee, S. Dhorda, M. Nguon, C. Lim, P. Amaratunga, C. Suon, S. Hien, T. T. Htut, Y. Faiz, M. A. Onyamboko, M. A. Mayxay, M. Newton, P. N. Tripura, R. Woodrow, C. J. Miotto, O. Kwiatkowski, D. P. Nosten, F. Day, N. P. J. Preiser, P. R. White, N. J. Dondorp, A. M. Fairhurst, R. M. Bozdech, Z. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Mok, S. Ashley, E. A. Ferreira, P. E. Zhu, L. Lin, Z. Yeo, T. Chotivanich, K. Imwong, M. Pukrittayakamee, S. Dhorda, M. Nguon, C. Lim, P. Amaratunga, C. Suon, S. Hien, T. T. Htut, Y. Faiz, M. A. Onyamboko, M. A. Mayxay, M. Newton, P. N. Tripura, R. Woodrow, C. J. Miotto, O. Kwiatkowski, D. P. Nosten, F. Day, N. P. J. Preiser, P. R. White, N. J. Dondorp, A. M. Fairhurst, R. M. Bozdech, Z. |
| author_sort | Mok, S. |
| collection | NTU |
| description | Artemisinin resistance in Plasmodium falciparum threatens global efforts to control and eliminate malaria. Polymorphisms in the kelch domain–carrying protein K13 are associated with artemisinin resistance, but the underlying molecular mechanisms are unknown. We analyzed the in vivo transcriptomes of 1043 P. falciparum isolates from patients with acute malaria and found that artemisinin resistance is associated with increased expression of unfolded protein response (UPR) pathways involving the major PROSC and TRiC chaperone complexes. Artemisinin-resistant parasites also exhibit decelerated progression through the first part of the asexual intraerythrocytic development cycle. These findings suggest that artemisinin-resistant parasites remain in a state of decelerated development at the young ring stage, whereas their up-regulated UPR pathways mitigate protein damage caused by artemisinin. The expression profiles of UPR-related genes also associate with the geographical origin of parasite isolates, further suggesting their role in emerging artemisinin resistance in the Greater Mekong Subregion. |
| first_indexed | 2024-10-01T07:56:24Z |
| format | Journal Article |
| id | ntu-10356/83802 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:56:24Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | ntu-10356/838022020-03-07T12:18:15Z Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance Mok, S. Ashley, E. A. Ferreira, P. E. Zhu, L. Lin, Z. Yeo, T. Chotivanich, K. Imwong, M. Pukrittayakamee, S. Dhorda, M. Nguon, C. Lim, P. Amaratunga, C. Suon, S. Hien, T. T. Htut, Y. Faiz, M. A. Onyamboko, M. A. Mayxay, M. Newton, P. N. Tripura, R. Woodrow, C. J. Miotto, O. Kwiatkowski, D. P. Nosten, F. Day, N. P. J. Preiser, P. R. White, N. J. Dondorp, A. M. Fairhurst, R. M. Bozdech, Z. School of Biological Sciences Malaria parasites Artemisinin resistance in Plasmodium falciparum threatens global efforts to control and eliminate malaria. Polymorphisms in the kelch domain–carrying protein K13 are associated with artemisinin resistance, but the underlying molecular mechanisms are unknown. We analyzed the in vivo transcriptomes of 1043 P. falciparum isolates from patients with acute malaria and found that artemisinin resistance is associated with increased expression of unfolded protein response (UPR) pathways involving the major PROSC and TRiC chaperone complexes. Artemisinin-resistant parasites also exhibit decelerated progression through the first part of the asexual intraerythrocytic development cycle. These findings suggest that artemisinin-resistant parasites remain in a state of decelerated development at the young ring stage, whereas their up-regulated UPR pathways mitigate protein damage caused by artemisinin. The expression profiles of UPR-related genes also associate with the geographical origin of parasite isolates, further suggesting their role in emerging artemisinin resistance in the Greater Mekong Subregion. NMRC (Natl Medical Research Council, S’pore) 2016-09-19T04:06:57Z 2019-12-06T15:32:22Z 2016-09-19T04:06:57Z 2019-12-06T15:32:22Z 2015 Journal Article Mok, S., Ashley, E. A., Ferreira, P. E., Zhu, L., Lin, Z., Yeo, T., Chotivanich, K., Imwong, M., Pukrittayakamee, S., Dhorda, M., Nguon, C., Lim, P., Amaratunga, C., Suon, S., Hien, T. T., Htut, Y., Faiz, M. A., Onyamboko, M. A., Mayxay, M., Newton, P. N., Tripura, R., Woodrow, C. J., Miotto, O., Kwiatkowski, D. P., Nosten, F., Day, N. P. J., Preiser, P. R., White, N. J., Dondorp, A. M., Fairhurst, R. M.,& Bozdech, Z. (2015). Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance. Science, 347(6220), 431-435. https://hdl.handle.net/10356/83802 http://hdl.handle.net/10220/41453 10.1126/science.1260403 en Science © 2016 American Association for the Advancement of Science. |
| spellingShingle | Malaria parasites Mok, S. Ashley, E. A. Ferreira, P. E. Zhu, L. Lin, Z. Yeo, T. Chotivanich, K. Imwong, M. Pukrittayakamee, S. Dhorda, M. Nguon, C. Lim, P. Amaratunga, C. Suon, S. Hien, T. T. Htut, Y. Faiz, M. A. Onyamboko, M. A. Mayxay, M. Newton, P. N. Tripura, R. Woodrow, C. J. Miotto, O. Kwiatkowski, D. P. Nosten, F. Day, N. P. J. Preiser, P. R. White, N. J. Dondorp, A. M. Fairhurst, R. M. Bozdech, Z. Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance |
| title | Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance |
| title_full | Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance |
| title_fullStr | Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance |
| title_full_unstemmed | Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance |
| title_short | Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance |
| title_sort | population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance |
| topic | Malaria parasites |
| url | https://hdl.handle.net/10356/83802 http://hdl.handle.net/10220/41453 |
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