ArticlePloS one2011
Fosmidomycin uptake into Plasmodium and Babesia-infected erythrocytes is facilitated by parasite-induced new permeability pathways.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 85 citations in OpenAlex.
- Article
- Repositioning Antibiotics Against Plasmodium falciparum RAD5 and WD11 as Novel Antimalarial Targets.Tropical medicine & international health : TM & IH · 2026Article
- Shared host, distinct invaders: metabolomic footprints of plasmodium and babesia in host red cells.Current opinion in hematology · 2025Review
- Studying Target-Engagement of Anti-Infectives by Solvent-Induced Protein Precipitation and Quantitative Mass Spectrometry.ACS infectious diseases · 2024Article
- 1-Deoxy-d-xylulose 5-phosphate reductoisomerase as target for anti Toxoplasma gondii agents: crystal structure, biochemical characterization and biological evaluation of inhibitors.The Biochemical journal · 2024Article
- Harnessing cholesterol uptake of malaria parasites for therapeutic applications.EMBO molecular medicine · 2024Article
- Critical interdependencies between Plasmodium nutrient flux and drugs.Trends in parasitology · 2023Review
- New insights into apicoplast metabolism in blood-stage malaria parasites.Current opinion in microbiology · 2023Review
- Over 40 Years of Fosmidomycin Drug Research: A Comprehensive Review and Future Opportunities.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Ring stage classification of Babesia microti and Plasmodium falciparum using optical diffraction 3D tomographic technique.Parasites & vectors · 2022Article
- Two apicoplast dwelling glycolytic enzymes provide key substrates for metabolic pathways in the apicoplast and are critical for Toxoplasma growth.PLoS pathogens · 2022Article
- The ferredoxin redox system - an essential electron distributing hub in the apicoplast of Apicomplexa.Trends in parasitology · 2022Review
- Plasmodium-a brief introduction to the parasites causing human malaria and their basic biology.Journal of physiological anthropology · 2021Review
- Targeting Host Glycolysis as a Strategy for Antimalarial Development.Frontiers in cellular and infection microbiology · 2021Article
- Plasmodium falciparum sexual parasites regulate infected erythrocyte permeability.Communications biology · 2020Article
- Metabolomics profiling reveals new aspects of dolichol biosynthesis in Plasmodium falciparum.Scientific reports · 2020Article
- Article
- Inhibitory Effects of Fosmidomycin AgainstFrontiers in cell and developmental biology · 2020Article
- Identification of Antimalarial Compounds That Require CLAG3 for Their Uptake byAntimicrobial agents and chemotherapy · 2019Article
- Acyloxybenzyl and Alkoxyalkyl Prodrugs of a Fosmidomycin Surrogate as Antimalarial and Antitubercular Agents.ACS medicinal chemistry letters · 2018Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHighly charged compounds typically suffer from low membrane permeability and thus are generally regarded as sub-optimal drug candidates. Nonetheless, the highly charged drug fosmidomycin and its more active methyl-derivative FR900098 have proven parasiticidal activity against erythrocytic stages of the malaria parasite Plasmodium falciparum. Both compounds target the isoprenoid biosynthesis pathway present in bacteria and plastid-bearing organisms, like apicomplexan parasites. Surprisingly, the compounds are inactive against a range of apicomplexans replicating in nucleated cells, including Toxoplasma gondii. METHODOLOGY/PRINCIPAL
findingsSince non-infected erythrocytes are impermeable for FR90098, we hypothesized that these drugs are taken up only by erythrocytes infected with Plasmodium. We provide evidence that radiolabeled FR900098 accumulates in theses cells as a consequence of parasite-induced new properties of the host cell, which coincide with an increased permeability of the erythrocyte membrane. Babesia divergens, a related parasite that also infects human erythrocytes and is also known to induce an increase in membrane permeability, displays a similar susceptibility and uptake behavior with regard to the drug. In contrast, Toxoplasma gondii-infected cells do apparently not take up the compounds, and the drugs are inactive against the liver stages of Plasmodium berghei, a mouse malaria parasite. CONCLUSIONS/SIGNIFICANCE: Our findings provide an explanation for the observed differences in activity of fosmidomycin and FR900098 against different Apicomplexa. These results have important implications for future screens aimed at finding new and safe molecular entities active against P. falciparum and related parasites. Our data provide further evidence that parasite-induced new permeability pathways may be exploited as routes for drug delivery.
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