ArticleAntimicrobial agents and chemotherapy2009
Plasmodium falciparum pfmdr1 amplification, mefloquine resistance, and parasite fitness.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 3 of them syntheses that pooled it.
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Who cites it
68 citing papers in PubMed, 3 syntheses or guidelines pooled it, 109 citations in OpenAlex.
- Mapping Antimalarial Drug Resistance in Mozambique: A Systematic Review ofInternational journal of molecular sciences · 2024Pooled it
- Assessment of copy number variation in genes related to drug resistance in Plasmodium vivax and Plasmodium falciparum isolates from the Brazilian Amazon and a systematic review of the literature.Malaria journal · 2017Pooled it
- Pooled it
- Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration.Malaria journal · 2016Trial
- Article
- Tolerance of Plasmodium falciparum mefloquine-resistant clinical isolates to mefloquine-piperaquine with implications for triple artemisinin-based combination therapies.Nature communications · 2025Article
- Nutrient stress dramatically increases malaria parasite clag2 copy number to increase host cell permeability and enable pathogen survival.PLoS pathogens · 2025Article
- Identification of a large anion channel required for digestive vacuole acidification and amino acid export in Plasmodium falciparum.PLoS biology · 2025Article
- Assessing fitness costs in malaria parasites: a comprehensive review and implications for drug resistance management.Malaria journal · 2025Review
- Trend of N86Y and Y184F Mutations in Pfmdr1 Gene in Children Under Seasonal Malaria Chemoprevention Coverage in Nanoro, Burkina Faso.Acta parasitologica · 2024Article
- Copy Number Variations of Plasmodium vivax DBP1, EBP/DBP2, and RBP2b in Ethiopians Who Are Duffy Positive and Duffy Negative.The Journal of infectious diseases · 2024Article
- Article
- Cultivation of Asexual Intraerythrocytic Stages ofPathogens (Basel, Switzerland) · 2023Review
- Article
- Prevalence and characterization of piperaquine, mefloquine and artemisinin derivatives triple-resistant Plasmodium falciparum in Cambodia.The Journal of antimicrobial chemotherapy · 2023Article
- Mechanistic basis for multidrug resistance and collateral drug sensitivity conferred to the malaria parasite by polymorphisms in PfMDR1 and PfCRT.PLoS biology · 2022Article
- Comparative Analysis of Plasmodium falciparum Genotyping via SNP Detection, Microsatellite Profiling, and Whole-Genome Sequencing.Antimicrobial agents and chemotherapy · 2022Article
- Evolution of Multidrug Resistance in Plasmodium falciparum: a Longitudinal Study of Genetic Resistance Markers in the Greater Mekong Subregion.Antimicrobial agents and chemotherapy · 2021Article
- Plasmodium falciparum resistance to ACTs: Emergence, mechanisms, and outlook.International journal for parasitology. Drugs and drug resistance · 2021Article
- Balanced impacts of fitness and drug pressure on the evolution of PfMDR1 polymorphisms in Plasmodium falciparum.Malaria journal · 2021Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mefloquine is widely used in combination with artemisinin derivatives for the treatment of falciparum malaria. Mefloquine resistance in Plasmodium falciparum has been related to increased copy numbers of multidrug-resistant gene 1 (pfmdr1). We studied the ex vivo dynamics of pfmdr1 gene amplification in culture-adapted P. falciparum in relation to mefloquine resistance and parasite fitness. A Thai P. falciparum isolate (isolate TM036) was assessed by the use of multiple genetic markers as a single genotype. Resistance was selected by exposure to stepwise increasing concentrations of mefloquine up to 30 ng/ml in continuous culture. The pfmdr1 gene copy numbers increased as susceptibility to mefloquine declined (P = 0.03). No codon mutations at positions 86, 184, 1034, 1042, and 1246 in the pfmdr1 gene were detected. Two subclones of selected parasites (average copy numbers, 2.3 and 3.1, respectively) showed a fitness disadvantage when they were grown together with the original parasites containing a single pfmdr1 gene copy in the absence of mefloquine; the multiplication rates were 6.3% and 8.7% lower, respectively (P < 0.01). Modeling of the dynamics of the pfmdr1 copy numbers over time in relation to the relative fitness of the parasites suggested that net pfmdr1 gene amplification from one to two copies occurs once in every 10(8) parasites and that amplification from two to three copies occurs once in every 10(3) parasites. pfmdr1 gene amplification in P. falciparum is a frequent event and confers mefloquine resistance. Parasites with multiple copies of the pfmdr1 gene have decreased survival fitness in the absence of drug pressure.
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