ArticlePloS one2010
Geographic structuring of the Plasmodium falciparum sarco(endo)plasmic reticulum Ca2+ ATPase (PfSERCA) gene diversity.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Possible Role of the CaMolecules (Basel, Switzerland) · 2019Article
- Molecular markers of anti-malarial drug resistance in Central, West and East African children with severe malaria.Malaria journal · 2017Article
- Reappraising the effects of artemisinin on the ATPase activity of PfATP6 and SERCA1a E255L expressed in Xenopus laevis oocytes.Nature structural & molecular biology · 2016Article
- Comparative genome analysis of Weissella ceti, an emerging pathogen of farm-raised rainbow trout.BMC genomics · 2015Article
- Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, Angola.Malaria journal · 2015Article
- Monitoring artemisinin resistance in Plasmodium falciparum: comparison of parasite clearance time by microscopy and real-time PCR and evaluation of mutations in Pfatpase6 gene in Odisha state of India.Parasitology research · 2015Article
- Molecular markers of anti-malarial drug resistance in southwest Ethiopia over time: regional surveillance from 2006 to 2013.Malaria journal · 2015Article
- An overview of malaria transmission from the perspective of Amazon Anopheles vectors.Memorias do Instituto Oswaldo Cruz · 2015Review
- Occurrence of pfatpase6 Single Nucleotide Polymorphisms Associated with Artemisinin Resistance among Field Isolates of Plasmodium falciparum in North-Eastern Tanzania.Malaria research and treatment · 2015Article
- Genetic diversity and lack of artemisinin selection signature on the Plasmodium falciparum ATP6 in the Greater Mekong Subregion.PloS one · 2013Article
- Characterization of the Plasmodium falciparum sarcoplasmic/endoplasmic reticulum Ca2+-ATPase gene in samples from Equatorial Guinea before implementation of artemisinin-based combination therapy.The American journal of tropical medicine and hygiene · 2013Article
- Molecular assessment of atpase6 mutations associated with artemisinin resistance among unexposed and exposed Plasmodium falciparum clinical isolates to artemisinin-based combination therapy.Malaria journal · 2012Article
- Lack of association of the S769N mutation in Plasmodium falciparum SERCA (PfATP6) with resistance to artemisinins.Antimicrobial agents and chemotherapy · 2012Article
- Artemether resistance in vitro is linked to mutations in PfATP6 that also interact with mutations in PfMDR1 in travellers returning with Plasmodium falciparum infections.Malaria journal · 2012Article
- Article
- Plasmodium falciparum produce lower infection intensities in local versus foreign Anopheles gambiae populations.PloS one · 2012Article
- Increased pfmdr1 copy number and sequence polymorphisms in Plasmodium falciparum isolates from Sudanese malaria patients treated with artemether-lumefantrine.Antimicrobial agents and chemotherapy · 2011Article
- Protein-based signatures of functional evolution in Plasmodium falciparum.BMC evolutionary biology · 2011Article
- Plasmodium falciparum isolates from southern Ghana exhibit polymorphisms in the SERCA-type PfATPase6 though sensitive to artesunate in vitro.Malaria journal · 2011Article
- Spontaneous mutations in the Plasmodium falciparum sarcoplasmic/ endoplasmic reticulum Ca2+-ATPase (PfATP6) gene among geographically widespread parasite populations unexposed to artemisinin-based combination therapies.Antimicrobial agents and chemotherapy · 2011Article
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Authors and funding
20 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Artemisinin, a thapsigargin-like sesquiterpene has been shown to inhibit the Plasmodium falciparum sarco/endoplasmic reticulum calcium-ATPase PfSERCA. To collect baseline pfserca sequence information before field deployment of Artemisinin-based Combination therapies that may select mutant parasites, we conducted a sequence analysis of 100 isolates from multiple sites in Africa, Asia and South America. Coding sequence diversity was large, with 29 mutated codons, including 32 SNPs (average of one SNP/115 bp), of which 19 were novel mutations. Most SNP detected in this study were clustered within a region in the cytosolic head of the protein. The PfSERCA functional domains were very well conserved, with non synonymous mutations located outside the functional domains, except for the S769N mutation associated in French Guiana with elevated IC(50) for artemether. The S769N mutation is located close to the hinge of the headpiece, which in other species modulates calcium affinity and in consequence efficacy of inhibitors, possibly linking calcium homeostasis to drug resistance. Genetic diversity was highest in Senegal, Brazil and French Guiana, and few mutations were identified in Asia. Population genetic analysis was conducted for a partial fragment of the gene encompassing nucleotide coordinates 87-2862 (unambiguous sequence available for 96 isolates). This supported a geographic clustering, with a separation between Old and New World samples and one dominant ancestral haplotype. Genetic drift alone cannot explain the observed polymorphism, suggesting that other evolutionary mechanisms are operating. One possible contributor could be the frequency of haemoglobinopathies that are associated with calcium dysregulation in the erythrocyte.
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