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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/47495
Title: Fitness Loss under Amino Acid Starvation in Artemisinin-Resistant Plasmodium falciparum Isolates from Cambodia
Authors: Duangkamon Bunditvorapoom
Theerarat Kochakarn
Namfon Kotanan
Charin Modchang
Krittikorn Kümpornsin
Duangkamon Loesbanluechai
Thanyaluk Krasae
Liwang Cui
Kesinee Chotivanich
Nicholas J. White
Prapon Wilairat
Olivo Miotto
Thanat Chookajorn
University of Oxford
Mahidol University
Faculty of Medicine, Siriraj Hospital, Mahidol University
Nuffield Department of Clinical Medicine
Wellcome Sanger Institute
Pennsylvania State University
Keywords: Multidisciplinary
Issue Date: 1-Dec-2018
Citation: Scientific Reports. Vol.8, No.1 (2018)
Abstract: © 2018, The Author(s). Artemisinin is the most rapidly effective drug for Plasmodium falciparum malaria treatment currently in clinical use. Emerging artemisinin-resistant parasites pose a great global health risk. At present, the level of artemisinin resistance is still relatively low with evidence pointing towards a trade-off between artemisinin resistance and fitness loss. Here we show that artemisinin-resistant P. falciparum isolates from Cambodia manifested fitness loss, showing fewer progenies during the intra-erythrocytic developmental cycle. The loss in fitness was exacerbated under the condition of low exogenous amino acid supply. The resistant parasites failed to undergo maturation, whereas their drug-sensitive counterparts were able to complete the erythrocytic cycle under conditions of amino acid deprivation. The artemisinin-resistant phenotype was not stable, and loss of the phenotype was associated with changes in the expression of a putative target, Exp1, a membrane glutathione transferase. Analysis of SNPs in haemoglobin processing genes revealed associations with parasite clearance times, suggesting changes in haemoglobin catabolism may contribute to artemisinin resistance. These findings on fitness and protein homeostasis could provide clues on how to contain emerging artemisinin-resistant parasites.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85052123124&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/47495
ISSN: 20452322
Appears in Collections:Scopus 2018

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