ArticleMolecular microbiology2017
A high susceptibility to redox imbalance of the transmissible stages of Plasmodium falciparum revealed with a luciferase-based mature gametocyte assay.
Article in Molecular microbiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Efficacy and safety of methylene blue in the treatment of malaria: a systematic review.BMC medicine · 2018Pooled it
- Revisiting Glutathione Transferases ofPharmaceuticals (Basel, Switzerland) · 2026Review
- An all-in-one pipeline for the in vitro discovery and in vivo testing of Plasmodium falciparum malaria transmission blocking drugs.Nature communications · 2025Article
- An improved multiplex RT-quantitative PCR assay can reveal sex-specific activity of transmission-blocking drugs on ex vivo gametocytes from Plasmodium falciparum asymptomatic infections.The Journal of antimicrobial chemotherapy · 2025Article
- Eliminating malaria transmission requires targeting immature and mature gametocytes through lipoidal uptake of antimalarials.Nature communications · 2024Article
- Safe drugs with high potential to block malaria transmission revealed by a spleen-mimetic screening.Nature communications · 2023Article
- AnFrontiers in cellular and infection microbiology · 2023Article
- Gametocyte-specific and all-blood-stage transmission-blocking chemotypes discovered from high throughput screening on Plasmodium falciparum gametocytes.Communications biology · 2022Article
- An Optimized Dihydrodibenzothiazepine Lead Compound (SBI-0797750) as a Potent and Selective Inhibitor of Plasmodium falciparum and P. vivax Glucose 6-Phosphate Dehydrogenase 6-Phosphogluconolactonase.Antimicrobial agents and chemotherapy · 2022Article
- The Nitrobenzoxadiazole Derivative NBDHEX Behaves asPharmaceuticals (Basel, Switzerland) · 2022Article
- The Role of the Iron Protoporphyrins Heme and Hematin in the Antimalarial Activity of Endoperoxide Drugs.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Streamlined and Robust Stage-Specific Profiling of Gametocytocidal Compounds AgainstFrontiers in cellular and infection microbiology · 2022Article
- The Artemiside-Artemisox-Artemisone-M1 Tetrad: Efficacies against Blood StagePharmaceutics · 2021Article
- Plasmodium falciparum LipB mutants display altered redox and carbon metabolism in asexual stages and cannot complete sporogony in Anopheles mosquitoes.International journal for parasitology · 2021Article
- Gene Polymorphisms AmongFrontiers in cellular and infection microbiology · 2021Article
- Evaluation of Nucleoside Analogs as Antimicrobials Targeting Unique Enzymes inPathogens (Basel, Switzerland) · 2020Article
- Inhibition of Resistance-Refractory P. falciparum Kinase PKG Delivers Prophylactic, Blood Stage, and Transmission-Blocking Antiplasmodial Activity.Cell chemical biology · 2020Article
- Combining Stage Specificity and Metabolomic Profiling to Advance Antimalarial Drug Discovery.Cell chemical biology · 2020Article
- Covalent Plasmodium falciparum-selective proteasome inhibitors exhibit a low propensity for generating resistance in vitro and synergize with multiple antimalarial agents.PLoS pathogens · 2019Article
- Bioassay-guided isolation and identification of gametocytocidal compounds from Artemisia afra (Asteraceae).Malaria journal · 2019Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
Abstract
The goal to prevent Plasmodium falciparum transmission from humans to mosquitoes requires the identification of targetable metabolic processes in the mature (stage V) gametocytes, the sexual stages circulating in the bloodstream. This task is complicated by the apparently low metabolism of these cells, which renders them refractory to most antimalarial inhibitors and constrains the development of specific and sensitive cell-based assays. Here, we identify and functionally characterize the regulatory regions of the P. falciparum gene PF3D7_1234700, encoding a CPW-WPC protein and named here Upregulated in Late Gametocytes (ULG8), which we have leveraged to express reporter genes in mature male and female gametocytes. Using transgenic parasites containing a pfULG8-luciferase cassette, we investigated the susceptibility of stage V gametocytes to compounds specifically affecting redox metabolism. Our results reveal a high sensitivity of mature gametocytes to the glutathione reductase inhibitor and redox cycler drug methylene blue (MB). Using isobologram analysis, we find that a concomitant inhibition of the parasite enzyme glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase, a key component of NADPH synthesis, potently synergizes MB activity. These data suggest that redox metabolism and detoxification activity play an unsuspected yet vital role in stage V gametocytes, rendering these cells exquisitely sensitive to decreases in NADPH concentration.
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Registered trials
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