Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response

Lei Zhu; Rob W. van der Pluijm; Michal Kucharski; Sourav Nayak; Jaishree Tripathi; Nicholas J. White; Nicholas P. J. Day; Abul Faiz; Aung Pyae Phyo; Chanaki Amaratunga; Dysoley Lek; Elizabeth A. Ashley; François Nosten; Frank Smithuis; Hagai Ginsburg; Lorenz von Seidlein; Khin Lin; Mallika Imwong; Kesinee Chotivanich; Mayfong Mayxay; Mehul Dhorda; Hoang Chau Nguyen; Thuy Nhien Thanh Nguyen; Olivo Miotto; Paul N. Newton; Podjanee Jittamala; Rupam Tripura; Sasithon Pukrittayakamee; Thomas J. Peto; Tran Tinh Hien; Arjen M. Dondorp; Zbynek Bozdech

doi:https://doi.org/10.1038/s42003-022-03215-0

Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response

Lei Zhu, Rob W. van der Pluijm, Michal Kucharski, Sourav Nayak, Jaishree Tripathi, Nicholas J. White, Nicholas P. J. Day, Abul Faiz, Aung Pyae Phyo, Chanaki Amaratunga, Dysoley Lek, Elizabeth A. Ashley, François Nosten, Frank Smithuis, Hagai Ginsburg, Lorenz von Seidlein, Khin Lin, Mallika Imwong, Kesinee Chotivanich, Mayfong MayxayMehul Dhorda, Hoang Chau Nguyen, Thuy Nhien Thanh Nguyen, Olivo Miotto, Paul N. Newton, Podjanee Jittamala, Rupam Tripura, Sasithon Pukrittayakamee, Thomas J. Peto, Tran Tinh Hien, Arjen M. Dondorp, Zbynek Bozdech

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

The emergence and spread of artemisinin-resistant Plasmodium falciparum, first in the Greater Mekong Subregion (GMS), and now in East Africa, is a major threat to global malaria elimination ambitions. To investigate the artemisinin resistance mechanism, transcriptome analysis was conducted of 577 P. falciparum isolates collected in the GMS between 2016–2018. A specific artemisinin resistance-associated transcriptional profile was identified that involves a broad but discrete set of biological functions related to proteotoxic stress, host cytoplasm remodelling, and REDOX metabolism. The artemisinin resistance-associated transcriptional profile evolved from initial transcriptional responses of susceptible parasites to artemisinin. The genetic basis for this adapted response is likely to be complex.

Original language	English
Article number	274
Journal	Communications Biology
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s42003-022-03215-0
Publication status	Published - 1 Dec 2022

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Zhu, L., van der Pluijm, R. W., Kucharski, M., Nayak, S., Tripathi, J., White, N. J., Day, N. P. J., Faiz, A., Phyo, A. P., Amaratunga, C., Lek, D., Ashley, E. A., Nosten, F., Smithuis, F., Ginsburg, H., von Seidlein, L., Lin, K., Imwong, M., Chotivanich, K., ... Bozdech, Z. (2022). Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response. Communications Biology, 5(1), Article 274. https://doi.org/10.1038/s42003-022-03215-0

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title = "Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response",

abstract = "The emergence and spread of artemisinin-resistant Plasmodium falciparum, first in the Greater Mekong Subregion (GMS), and now in East Africa, is a major threat to global malaria elimination ambitions. To investigate the artemisinin resistance mechanism, transcriptome analysis was conducted of 577 P. falciparum isolates collected in the GMS between 2016–2018. A specific artemisinin resistance-associated transcriptional profile was identified that involves a broad but discrete set of biological functions related to proteotoxic stress, host cytoplasm remodelling, and REDOX metabolism. The artemisinin resistance-associated transcriptional profile evolved from initial transcriptional responses of susceptible parasites to artemisinin. The genetic basis for this adapted response is likely to be complex.",

author = "Lei Zhu and {van der Pluijm}, {Rob W.} and Michal Kucharski and Sourav Nayak and Jaishree Tripathi and White, {Nicholas J.} and Day, {Nicholas P. J.} and Abul Faiz and Phyo, {Aung Pyae} and Chanaki Amaratunga and Dysoley Lek and Ashley, {Elizabeth A.} and Fran{\c c}ois Nosten and Frank Smithuis and Hagai Ginsburg and {von Seidlein}, Lorenz and Khin Lin and Mallika Imwong and Kesinee Chotivanich and Mayfong Mayxay and Mehul Dhorda and Nguyen, {Hoang Chau} and Nguyen, {Thuy Nhien Thanh} and Olivo Miotto and Newton, {Paul N.} and Podjanee Jittamala and Rupam Tripura and Sasithon Pukrittayakamee and Peto, {Thomas J.} and Hien, {Tran Tinh} and Dondorp, {Arjen M.} and Zbynek Bozdech",

note = "Funding Information: We would like to thank all members of the Tracking Resistance to Artemisinin Collaboration for providing access to clinical samples used in this study as well as all patients that have agreed to participate in this TRACII clinical trials. We also would like to thank Sachel Mok for providing the parasite reference pool and Cholrawee Promnarate, Nakarin Aud-Ai for coordinating field specimen collection. This research was funded by Singapore National Medical Research Council grant #NMRC/OFIRG/0040/2017 and Singapore Ministry of education grant #MOE2019-T3-1-007 and #MOE2017-T2-2-030 (S) awarded to Z. Bozdech. Moreover, A.D. coordinated funding for the TRACII epidemiology studies funded by DFID (FCDO): Artemisinin Resistant Malaria Research Programme (TRAC). DFID PO 5408 and Wellcome Trust: MOP Thailand Core award 220211/Z/20/Z and 220211/A/20/Z. Funding Information: We would like to thank all members of the Tracking Resistance to Artemisinin Collaboration for providing access to clinical samples used in this study as well as all patients that have agreed to participate in this TRACII clinical trials. We also would like to thank Sachel Mok for providing the parasite reference pool and Cholrawee Promnarate, Nakarin Aud-Ai for coordinating field specimen collection. This research was funded by Singapore National Medical Research Council grant #NMRC/OFIRG/0040/2017 and Singapore Ministry of education grant #MOE2019-T3-1-007 and #MOE2017-T2-2-030 (S) awarded to Z. Bozdech. Moreover, A.D. coordinated funding for the TRACII epidemiology studies funded by DFID (FCDO): Artemisinin Resistant Malaria Research Programme (TRAC). DFID PO 5408 and Wellcome Trust: MOP Thailand Core award 220211/Z/20/Z and 220211/A/20/Z. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

day = "1",

doi = "https://doi.org/10.1038/s42003-022-03215-0",

language = "English",

volume = "5",

journal = "Communications Biology",

issn = "2399-3642",

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Zhu, L, van der Pluijm, RW, Kucharski, M, Nayak, S, Tripathi, J, White, NJ, Day, NPJ, Faiz, A, Phyo, AP, Amaratunga, C, Lek, D, Ashley, EA, Nosten, F, Smithuis, F, Ginsburg, H, von Seidlein, L, Lin, K, Imwong, M, Chotivanich, K, Mayxay, M, Dhorda, M, Nguyen, HC, Nguyen, TNT, Miotto, O, Newton, PN, Jittamala, P, Tripura, R, Pukrittayakamee, S, Peto, TJ, Hien, TT, Dondorp, AM & Bozdech, Z 2022, 'Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response', Communications Biology, vol. 5, no. 1, 274. https://doi.org/10.1038/s42003-022-03215-0

TY - JOUR

T1 - Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response

AU - Zhu, Lei

AU - van der Pluijm, Rob W.

AU - Kucharski, Michal

AU - Nayak, Sourav

AU - Tripathi, Jaishree

AU - White, Nicholas J.

AU - Day, Nicholas P. J.

AU - Faiz, Abul

AU - Phyo, Aung Pyae

AU - Amaratunga, Chanaki

AU - Lek, Dysoley

AU - Ashley, Elizabeth A.

AU - Nosten, François

AU - Smithuis, Frank

AU - Ginsburg, Hagai

AU - von Seidlein, Lorenz

AU - Lin, Khin

AU - Imwong, Mallika

AU - Chotivanich, Kesinee

AU - Mayxay, Mayfong

AU - Dhorda, Mehul

AU - Nguyen, Hoang Chau

AU - Nguyen, Thuy Nhien Thanh

AU - Miotto, Olivo

AU - Newton, Paul N.

AU - Jittamala, Podjanee

AU - Tripura, Rupam

AU - Pukrittayakamee, Sasithon

AU - Peto, Thomas J.

AU - Hien, Tran Tinh

AU - Dondorp, Arjen M.

AU - Bozdech, Zbynek

N1 - Funding Information: We would like to thank all members of the Tracking Resistance to Artemisinin Collaboration for providing access to clinical samples used in this study as well as all patients that have agreed to participate in this TRACII clinical trials. We also would like to thank Sachel Mok for providing the parasite reference pool and Cholrawee Promnarate, Nakarin Aud-Ai for coordinating field specimen collection. This research was funded by Singapore National Medical Research Council grant #NMRC/OFIRG/0040/2017 and Singapore Ministry of education grant #MOE2019-T3-1-007 and #MOE2017-T2-2-030 (S) awarded to Z. Bozdech. Moreover, A.D. coordinated funding for the TRACII epidemiology studies funded by DFID (FCDO): Artemisinin Resistant Malaria Research Programme (TRAC). DFID PO 5408 and Wellcome Trust: MOP Thailand Core award 220211/Z/20/Z and 220211/A/20/Z. Funding Information: We would like to thank all members of the Tracking Resistance to Artemisinin Collaboration for providing access to clinical samples used in this study as well as all patients that have agreed to participate in this TRACII clinical trials. We also would like to thank Sachel Mok for providing the parasite reference pool and Cholrawee Promnarate, Nakarin Aud-Ai for coordinating field specimen collection. This research was funded by Singapore National Medical Research Council grant #NMRC/OFIRG/0040/2017 and Singapore Ministry of education grant #MOE2019-T3-1-007 and #MOE2017-T2-2-030 (S) awarded to Z. Bozdech. Moreover, A.D. coordinated funding for the TRACII epidemiology studies funded by DFID (FCDO): Artemisinin Resistant Malaria Research Programme (TRAC). DFID PO 5408 and Wellcome Trust: MOP Thailand Core award 220211/Z/20/Z and 220211/A/20/Z. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12/1

Y1 - 2022/12/1

N2 - The emergence and spread of artemisinin-resistant Plasmodium falciparum, first in the Greater Mekong Subregion (GMS), and now in East Africa, is a major threat to global malaria elimination ambitions. To investigate the artemisinin resistance mechanism, transcriptome analysis was conducted of 577 P. falciparum isolates collected in the GMS between 2016–2018. A specific artemisinin resistance-associated transcriptional profile was identified that involves a broad but discrete set of biological functions related to proteotoxic stress, host cytoplasm remodelling, and REDOX metabolism. The artemisinin resistance-associated transcriptional profile evolved from initial transcriptional responses of susceptible parasites to artemisinin. The genetic basis for this adapted response is likely to be complex.

AB - The emergence and spread of artemisinin-resistant Plasmodium falciparum, first in the Greater Mekong Subregion (GMS), and now in East Africa, is a major threat to global malaria elimination ambitions. To investigate the artemisinin resistance mechanism, transcriptome analysis was conducted of 577 P. falciparum isolates collected in the GMS between 2016–2018. A specific artemisinin resistance-associated transcriptional profile was identified that involves a broad but discrete set of biological functions related to proteotoxic stress, host cytoplasm remodelling, and REDOX metabolism. The artemisinin resistance-associated transcriptional profile evolved from initial transcriptional responses of susceptible parasites to artemisinin. The genetic basis for this adapted response is likely to be complex.

UR - http://www.scopus.com/inward/record.url?scp=85127289697&partnerID=8YFLogxK

U2 - https://doi.org/10.1038/s42003-022-03215-0

DO - https://doi.org/10.1038/s42003-022-03215-0

M3 - Article

C2 - 35347215

SN - 2399-3642

VL - 5

JO - Communications Biology

JF - Communications Biology

IS - 1

M1 - 274

ER -

Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response

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