ArticleMalaria journal2017
Functional analysis of Plasmodium falciparum subpopulations associated with artemisinin resistance in Cambodia.
Article in Malaria journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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Who cites it
12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.
- Identification of Co-Existing Mutations and Gene Expression Trends Associated With K13-Mediated Artemisinin Resistance inFrontiers in genetics · 2022Pooled it
- Pooled it
- Article
- Cytoprotective autophagy as a pro-survival strategy in ART-resistant malaria parasites.Cell death discovery · 2023Article
- Mutation in the Plasmodium falciparum BTB/POZ Domain of K13 Protein Confers Artemisinin Resistance.Antimicrobial agents and chemotherapy · 2022Article
- Integration of population and functional genomics to understand mechanisms of artemisinin resistance in Plasmodium falciparum.International journal for parasitology. Drugs and drug resistance · 2021Article
- Article
- Optimization of parasite DNA enrichment approaches to generate whole genome sequencing data for Plasmodium falciparum from low parasitaemia samples.Malaria journal · 2020Article
- Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential.Genome medicine · 2020Article
- Origin and Spread of Evolving Artemisinin-ResistantThe American journal of tropical medicine and hygiene · 2019Review
- Pre-clinical study of iron oxide nanoparticles fortified artesunate for efficient targeting of malarial parasite.EBioMedicine · 2019Article
- Mechanisms of artemisinin resistance in Plasmodium falciparum malaria.Current opinion in pharmacology · 2018Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundPlasmodium falciparum malaria is one of the most widespread parasitic infections in humans and remains a leading global health concern. Malaria elimination efforts are threatened by the emergence and spread of resistance to artemisinin-based combination therapy, the first-line treatment of malaria. Promising molecular markers and pathways associated with artemisinin drug resistance have been identified, but the underlying molecular mechanisms of resistance remains unknown. The genomic data from early period of emergence of artemisinin resistance (2008-2011) was evaluated, with aim to define k13 associated genetic background in Cambodia, the country identified as epicentre of anti-malarial drug resistance, through characterization of 167 parasite isolates using a panel of 21,257 SNPs.
resultsEight subpopulations were identified suggesting a process of acquisition of artemisinin resistance consistent with an emergence-selection-diffusion model, supported by the shifting balance theory. Identification of population specific mutations facilitated the characterization of a core set of 57 background genes associated with artemisinin resistance and associated pathways. The analysis indicates that the background of artemisinin resistance was not acquired after drug pressure, rather is the result of fixation followed by selection on the daughter subpopulations derived from the ancestral population.
conclusionsFunctional analysis of artemisinin resistance subpopulations illustrates the strong interplay between ubiquitination and cell division or differentiation in artemisinin resistant parasites. The relationship of these pathways with the P. falciparum resistant subpopulation and presence of drug resistance markers in addition to k13, highlights the major role of admixed parasite population in the diffusion of artemisinin resistant background. The diffusion of resistant genes in the Cambodian admixed population after selection resulted from mating of gametocytes of sensitive and resistant parasite populations.
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