Publication: Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription
Accepted Date
2011-08-03
Issued Date
2011-08-03
Copyright Date
2011
Resource Type
Language
eng
ISSN
1471-2164 (electronic)
Rights
Mahidol University
Rights Holder(s)
BioMed Central
Bibliographic Citation
Mok S, Imwong M, Mackinnon MJ, Sim J, Ramadoss R, Yi P, et al. Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription. BMC Genomics.
2011 Aug 3;12:391.
Suggested Citation
Mok, Sachel, Mallika Imwong, มัลลิกา อิ่มวงศ์, Mackinnon, Margaret J., Sim, Joan, Ramadoss, Ramya, Yi, Poravuth, Mayfong Mayxay, Kesinee Chotivanich, เกศินี โชติวานิช, Liong, Kek-Yee, Russell, Bruce, Socheat, Duong, Newton, Paul N., Day, Nicholas P.J., White, Nicholas J., Preiser, Peter R., Nosten, François, Dondorp, Arjen M., Bozdech, Zbynek Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription. Mok S, Imwong M, Mackinnon MJ, Sim J, Ramadoss R, Yi P, et al. Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription. BMC Genomics.
2011 Aug 3;12:391.. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/727
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription
Author(s)
Mok, Sachel
Mallika Imwong
มัลลิกา อิ่มวงศ์
Mackinnon, Margaret J.
Sim, Joan
Ramadoss, Ramya
Yi, Poravuth
Mayfong Mayxay
Kesinee Chotivanich
เกศินี โชติวานิช
Liong, Kek-Yee
Russell, Bruce
Socheat, Duong
Newton, Paul N.
Day, Nicholas P.J.
White, Nicholas J.
Preiser, Peter R.
Nosten, François
Dondorp, Arjen M.
Bozdech, Zbynek
Mallika Imwong
มัลลิกา อิ่มวงศ์
Mackinnon, Margaret J.
Sim, Joan
Ramadoss, Ramya
Yi, Poravuth
Mayfong Mayxay
Kesinee Chotivanich
เกศินี โชติวานิช
Liong, Kek-Yee
Russell, Bruce
Socheat, Duong
Newton, Paul N.
Day, Nicholas P.J.
White, Nicholas J.
Preiser, Peter R.
Nosten, François
Dondorp, Arjen M.
Bozdech, Zbynek
Corresponding Author(s)
Abstract
BACKGROUND: Artemisinin resistance in Plasmodium falciparum malaria has emerged
in Western Cambodia. This is a major threat to global plans to control and
eliminate malaria as the artemisinins are a key component of antimalarial
treatment throughout the world. To identify key features associated with the
delayed parasite clearance phenotype, we employed DNA microarrays to profile the
physiological gene expression pattern of the resistant isolates.
RESULTS: In the ring and trophozoite stages, we observed reduced expression of
many basic metabolic and cellular pathways which suggests a slower growth and
maturation of these parasites during the first half of the asexual
intraerythrocytic developmental cycle (IDC). In the schizont stage, there is an
increased expression of essentially all functionalities associated with protein
metabolism which indicates the prolonged and thus increased capacity of protein
synthesis during the second half of the resistant parasite IDC. This modulation
of the P. falciparum intraerythrocytic transcriptome may result from differential
expression of regulatory proteins such as transcription factors or chromatin
remodeling associated proteins. In addition, there is a unique and uniform copy
number variation pattern in the Cambodian parasites which may represent an
underlying genetic background that contributes to the resistance phenotype.
CONCLUSIONS: The decreased metabolic activities in the ring stages are consistent
with previous suggestions of higher resilience of the early developmental stages
to artemisinin. Moreover, the increased capacity of protein synthesis and protein
turnover in the schizont stage may contribute to artemisinin resistance by
counteracting the protein damage caused by the oxidative stress and/or protein
alkylation effect of this drug. This study reports the first global
transcriptional survey of artemisinin resistant parasites and provides insight to
the complexities of the molecular basis of pathogens with drug resistance
phenotypes in vivo.