Fitness loss under amino acid starvation in artemisinin-resistant Plasmodium falciparum isolates from Cambodia

Bunditvorapoom, D. et al. (2018) Fitness loss under amino acid starvation in artemisinin-resistant Plasmodium falciparum isolates from Cambodia. Scientific Reports, 8(1), 12622. (doi: 10.1038/s41598-018-30593-5) (PMID:30135481) (PMCID:PMC6105667)

Abstract

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.

• Item Type: Articles
• Additional Information: The work in the Chookajorn laboratory was supported by Thailand Research Fund-Mahidol University (RSA5880062) and the Faculty of Tropical Medicine, Mahidol University. DB was supported by a scholarship (D43TW006571) from the Fogarty International Center, National Institutes of Health (NIH), USA. LC was supported by grants (U19AI089672 and R01AI128940) from National Institute of Allergy and Infectious Diseases, NIH. TKo was supported by the Royal Golden Jubilee Ph.D. Program (Grant No. PHD/0204/2552).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Loesbanluechai, Ms Duangkamon
• Authors: Bunditvorapoom, D., Kochakarn, T., Kotanan, N., Modchang, C., Kümpornsin, K., Loesbanluechai, D., Krasae, T., Cui, L., Chotivanich, K., White, N. J., Wilairat, P., Miotto, O., and Chookajorn, T.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © The Author(s) 2018
• First Published: First published in Scientific Reports 8(1):12622
• Publisher Policy: Reproduced under a Creative Commons license