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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription
BMC Genomics, Volume 12, Article 391, Year 2011
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Description
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. © 2011 Mok et al; licensee BioMed Central Ltd.
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Authors & Co-Authors
Mok, Sachel
Singapore, Singapore City
School of Biological Sciences
Imwong, Mallika
Thailand, Nakhon Pathom
Mahidol University
MacKinnon, Margaret J.
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Sim, Joan
Singapore, Singapore City
School of Biological Sciences
Ramadoss, Ramya
Singapore, Singapore City
School of Biological Sciences
Yi, Poravuth
Cambodia, Phnom Penh
National Center for Parasitology, Entomology and Malaria Control
Mayxay, Mayfong
Democratic Republic Congo, Vientiane
Wellcome Trust-mahosot Hospital-oxford University Tropical Medicine Research Collaboration
Democratic Republic Congo
University of Health Sciences
Chotivanich, Kesinee T.
Thailand, Nakhon Pathom
Mahidol University
Liong, Kek Yee
Singapore, Singapore City
School of Biological Sciences
Russell, Bruce M.
Singapore, Singapore City
A-star, Singapore Immunology Network
Socheat, Duong
Cambodia, Phnom Penh
National Center for Parasitology, Entomology and Malaria Control
Newton, Paul N.
Democratic Republic Congo, Vientiane
Wellcome Trust-mahosot Hospital-oxford University Tropical Medicine Research Collaboration
United Kingdom, Oxford
Churchill Hospital
Day, Nichloas P.J.
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Oxford
Churchill Hospital
White, Nicholas J.
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Oxford
Churchill Hospital
Preiser, Peter R.
Singapore, Singapore City
School of Biological Sciences
Nosten, François Henry
United Kingdom, Oxford
Churchill Hospital
Thailand, Mae Sod
Shoklo Malaria Research Unit
Dondorp, A. M.
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Oxford
Churchill Hospital
Bozdech, Zbynek
Singapore, Singapore City
School of Biological Sciences
Statistics
Citations: 191
Authors: 18
Affiliations: 9
Identifiers
Doi:
10.1186/1471-2164-12-391
e-ISSN:
14712164
Research Areas
Genetics And Genomics
Infectious Diseases
Noncommunicable Diseases
Study Design
Cross Sectional Study
Study Approach
Quantitative