Publication: Fitness Loss under Amino Acid Starvation in Artemisinin-Resistant Plasmodium falciparum Isolates from Cambodia
Issued Date
2018-12-01
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ISSN
20452322
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2-s2.0-85052123124
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Mahidol University
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SCOPUS
Bibliographic Citation
Scientific Reports. Vol.8, No.1 (2018)
Suggested Citation
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 Fitness Loss under Amino Acid Starvation in Artemisinin-Resistant Plasmodium falciparum Isolates from Cambodia. Scientific Reports. Vol.8, No.1 (2018). doi:10.1038/s41598-018-30593-5 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/47495
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Title
Fitness Loss under Amino Acid Starvation in Artemisinin-Resistant Plasmodium falciparum Isolates from Cambodia
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.