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The Plasmodium berghei RC strain is highly diverged and harbors putatively novel drug resistance variants
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Document Title
The Plasmodium berghei RC strain is highly diverged and harbors putatively novel drug resistance variants
Author
Songsungthong W., Kulawonganunchai S., Wilantho A., Tongsima S., Koonyosying P., Uthaipibull C., Kamchonwongpaisan S., Shaw P.J.
Name from Authors Collection
Scopus Author ID
55760394500
Affiliations
Protein-Ligand Engineering and Molecular Biology Laboratory, Medical Molecular Biology Research Unit, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand; Biomolecular Analysis and Application Laboratory, Biosensing Technology Research Unit, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand; Biostatistics and Bioinformatics Laboratory, Genome Technology Research Unit, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand
Type
Article
Source Title
PeerJ
ISSN
21678359
Year
2017
Volume
2017
Issue
10
Open Access
All Open Access, Gold, Green
Publisher
PeerJ Inc.
DOI
10.7717/peerj.3766
Format
Abstract
Background: The current first line drugs for treating uncomplicated malaria are artemisinin (ART) combination therapies. However, Plasmodium falciparum parasites resistant to ART and partner drugs are spreading, which threatens malaria control efforts. Rodent malaria species are useful models for understanding antimalarial resistance, in particular genetic variants responsible for cross resistance to different compounds. Methods: The Plasmodium berghei RC strain (PbRC) is described as resistant to different antimalarials, including chloroquine (CQ) and ART. In an attempt to identify the genetic basis for the antimalarial resistance trait in PbRC, its genome was sequenced and compared with five other previously sequenced P. berghei strains. Results: We found that PbRC is eight-fold less sensitive to the ART derivative artesunate than the reference strain PbANKA. The genome of PbRC is markedly different from other strains, and 6,974 single nucleotide variants private to PbRC were identified. Among these PbRC private variants, non-synonymous changes were identified in genes known to modulate antimalarial sensitivity in rodent malaria species, including notably the ubiquitin carboxyl-terminal hydrolase 1 gene. However, no variants were found in some genes with strong evidence of association with ART resistance in P. falciparum such as K13 propeller protein. Discussion: The variants identified in PbRC provide insight into P. berghei genome diversity and genetic factors that could modulate CQ and ART resistance in Plasmodium spp. © 2017 Songsungthong et al.
Keyword
Artemisinin | Chloroquine | Genome | Malaria | Plasmodium berghei RC
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
National Research Council of Thailand; National Center for Genetic Engineering and Biotechnology
License
N/A
Rights
N/A
Publication Source
Scopus