The mechanism of artemisinin resistance of Plasmodium falciparum malaria parasites originates in their initial transcriptional response

  1. Lei Zhu
  2. Rob W. van der Pluijm
  3. Michal Kucharski
  4. Sourav Nayak
  5. Jaishree Tripathi
  6. François Nosten
  7. Abul Faiz
  8. Chanaki Amaratunga
  9. Dysoley Lek
  10. Elizabeth A Ashley
  11. Frank Smithuis
  12. Aung Pyae Phyo
  13. Khin Lin
  14. Mallika Imwong
  15. Mayfong Mayxay
  16. Mehul Dhorda
  17. Nguyen Hoang Chau
  18. Nhien Nguyen Thanh Thuy
  19. Paul N Newton
  20. Podjanee Jittamala
  21. Rupam Tripura
  22. Sasithon Pukrittayakamee
  23. Thomas J Peto
  24. Olivo Miotto
  25. Lorenz von Seidlein
  26. Tran Tinh Hien
  27. Hagai Ginsburg
  28. Nicholas PJ Day
  29. Nicholas J. White
  30. Arjen M Dondorp
  31. Zbynek Bozdech
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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 eliminations 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 remodeling 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.

One sentence summary

The transcriptional profile that characterize artemisinin resistant infections with malaria parasites Plasmodium falciparum originates in the initial transcriptional response to the drug.

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