ArticleAntimicrobial agents and chemotherapy2014
Fatty acid synthesis and pyruvate metabolism pathways remain active in dihydroartemisinin-induced dormant ring stages of Plasmodium falciparum.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Identification of Co-Existing Mutations and Gene Expression Trends Associated With K13-Mediated Artemisinin Resistance inFrontiers in genetics · 2022Pooled it
- Single-cell transcriptional changes of artemisinin-sensitive K13Frontiers in cellular and infection microbiology · 2026Article
- Fluorescence-based bioassay for the detection of changes in mitochondrial physiology during artemisinin-induced growth arrest of blood-stage Plasmodium falciparum.Scientific reports · 2025Article
- Hybrid Molecules as Efficient Drugs against Multidrug-Resistant Malaria Parasites.ChemMedChem · 2025Review
- Isolation and characterization ofAntimicrobial agents and chemotherapy · 2025Article
- Artemisinin-resistant malaria.Clinical microbiology reviews · 2024Review
- Article
- Progressive heterogeneity of enlarged and irregularly shaped apicoplasts inbioRxiv : the preprint server for biology · 2024Article
- The artemisinin-induced dormant stages of Plasmodium falciparum exhibit hallmarks of cellular quiescence/senescence and drug resilience.Nature communications · 2024Article
- Molecular Mechanisms of Persistence in Protozoan Parasites.Microorganisms · 2023Review
- Chemogenomic Profiling of a Plasmodium falciparum Transposon Mutant Library Reveals Shared Effects of Dihydroartemisinin and Bortezomib on Lipid Metabolism and Exported Proteins.Microbiology spectrum · 2023Article
- Secondary Metabolites Isolated fromMetabolites · 2023Review
- Article
- Slow growing behavior in African trypanosomes during adipose tissue colonization.Nature communications · 2022Article
- Chloroquine-susceptible and -resistant Plasmodium falciparum strains survive high chloroquine concentrations by becoming dormant but are eliminated by prolonged exposure.The Journal of antimicrobial chemotherapy · 2022Article
- Impact of Drug Pressure versus Limited Access to Drug in Malaria Control: The Dilemma.Medicines (Basel, Switzerland) · 2022Review
- Protecting future antimalarials from the trap of resistance: Lessons from artemisinin-based combination therapy (ACT) failures.Journal of pharmaceutical analysis · 2021Review
- Plasmodium falciparum resistance to ACTs: Emergence, mechanisms, and outlook.International journal for parasitology. Drugs and drug resistance · 2021Article
- Article
- Orthosteric-allosteric dual inhibitors of PfHT1 as selective antimalarial agents.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Artemisinin (ART)-based combination therapy (ACT) is used as the first-line treatment of uncomplicated falciparum malaria worldwide. However, despite high potency and rapid action, there is a high rate of recrudescence associated with ART monotherapy or ACT long before the recent emergence of ART resistance. ART-induced ring-stage dormancy and recovery have been implicated as possible causes of recrudescence; however, little is known about the characteristics of dormant parasites, including whether dormant parasites are metabolically active. We investigated the transcription of 12 genes encoding key enzymes in various metabolic pathways in P. falciparum during dihydroartemisinin (DHA)-induced dormancy and recovery. Transcription analysis showed an immediate downregulation for 10 genes following exposure to DHA but continued transcription of 2 genes encoding apicoplast and mitochondrial proteins. Transcription of several additional genes encoding apicoplast and mitochondrial proteins, particularly of genes encoding enzymes in pyruvate metabolism and fatty acid synthesis pathways, was also maintained. Additions of inhibitors for biotin acetyl-coenzyme A (CoA) carboxylase and enoyl-acyl carrier reductase of the fatty acid synthesis pathways delayed the recovery of dormant parasites by 6 and 4 days, respectively, following DHA treatment. Our results demonstrate that most metabolic pathways are downregulated in DHA-induced dormant parasites. In contrast, fatty acid and pyruvate metabolic pathways remain active. These findings highlight new targets to interrupt recovery of parasites from ART-induced dormancy and to reduce the rate of recrudescence following ART treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.