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

被引：0

作者：

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

机构：

[1] Nanyang Technological University,School of Biological Sciences

[2] Mahidol University,Mahidol

[3] University of Oxford,Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine

[4] University of Amsterdam,Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine

[5] Ramu Upazila Health Complex,Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Academic Medical Center

[6] Malaria Research Group and Dev Care Foundation,Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases

[7] Myanmar Oxford Clinical Research Unit,Shoklo Malaria Research Unit, Mahidol

[8] National Institutes of Health,Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine

[9] National Centre for Parasitology,The Alexander Silberman Institute of Life Science

[10] Entomology and Malaria Control,Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine

[11] Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit,Institute of Research and Education Development (IRED)

[12] Mahidol University,Oxford University Clinical Research Unit

[13] Hebrew University of Jerusalem,Medical Research Council (MRC) Centre for Genomics and Global Health

[14] Department of Medical Research,Department of Clinical Tropical Medicine, Faculty of Tropical Medicine

[15] Mahidol University,undefined

[16] University of Health Sciences,undefined

[17] Ministry of Health,undefined

[18] WorldWide Antimalarial Resistance Network – Asia-Pacific Regional Centre,undefined

[19] Hospital for Tropical Diseases,undefined

[20] University of Oxford,undefined

[21] Wellcome Trust Sanger Institute,undefined

[22] Mahidol University,undefined

[23] The Royal Society of Thailand,undefined

[24] Dusit,undefined

来源：

Communications Biology | / 5卷

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摘要：

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.

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