ArticleThe Journal of experimental medicine2011
Apicoplast isoprenoid precursor synthesis and the molecular basis of fosmidomycin resistance in Toxoplasma gondii.
Article in The Journal of experimental medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 156 citations in OpenAlex.
- Article
- The mevalonate and methylerythritol phosphate pathways as therapeutic targets in protozoan parasites: from moonlighting enzymes to metabolic plasticity.Cell communication and signaling : CCS · 2026Review
- Effect of Stereochemistry on the Antiplasmodial Activity and Metabolomic Profile of Novel Tadalafil Analogues.ACS medicinal chemistry letters · 2026Article
- Transporters, an important but poorly studied area of Toxoplasma gondii.Parasites & vectors · 2026Review
- Old drugs, new weapons: current trends in repurposing therapies against antimicrobial resistance.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026Review
- The early human interferon gamma response to Toxoplasma gondii is driven by Vγ9Vδ2 T-cell sensing of host phosphoantigens and subsequent NK-cell activation.PLoS pathogens · 2025Article
- TgGloL is an atypical glyoxalase/VOC domain-containing apicoplast protein that is important for the growth ofMolecular biology of the cell · 2025Article
- Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle.Nature communications · 2025Article
- A kalihinol analog disrupts apicoplast function and vesicular trafficking inScience (New York, N.Y.) · 2024Article
- Design and synthesis of non-hydroxamate lipophilic inhibitors of 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR):RSC advances · 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
- A pyruvate transporter in the apicoplast of apicomplexan parasites.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Drug Repurposing in the Chemotherapy of Infectious Diseases.Molecules (Basel, Switzerland) · 2024Review
- Beyond the MEP Pathway: A novel kinase required for prenol utilization by malaria parasites.PLoS pathogens · 2024Article
- The interdependence of isoprenoid synthesis and apicoplast biogenesis in malaria parasites.PLoS pathogens · 2023Article
- The apicoplast is important for the viability and persistence ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- New insights into apicoplast metabolism in blood-stage malaria parasites.Current opinion in microbiology · 2023Review
- Protein kinases on carbon metabolism: potential targets for alternative chemotherapies against toxoplasmosis.Frontiers in cellular and infection microbiology · 2023Review
- Over 40 Years of Fosmidomycin Drug Research: A Comprehensive Review and Future Opportunities.Pharmaceuticals (Basel, Switzerland) · 2022Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedStrurm, Angelika [corrected to Sturm, Angelika]
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Apicomplexa are important pathogens that include the causative agents of malaria, toxoplasmosis, and cryptosporidiosis. Apicomplexan parasites contain a relict chloroplast, the apicoplast. The apicoplast is indispensable and an attractive drug target. The apicoplast is home to a 1-deoxy-D-xylulose-5-phosphate (DOXP) pathway for the synthesis of isoprenoid precursors. This pathway is believed to be the most conserved function of the apicoplast, and fosmidomycin, a specific inhibitor of the pathway, is an effective antimalarial. Surprisingly, fosmidomycin has no effect on most other apicomplexans. Using Toxoplasma gondii, we establish that the pathway is essential in parasites that are highly fosmidomycin resistant. We define the molecular basis of resistance and susceptibility, experimentally testing various host and parasite contributions in T. gondii and Plasmodium. We demonstrate that in T. gondii the parasite plasma membrane is a critical barrier to drug uptake. In strong support of this hypothesis, we engineer de novo drug-sensitive T. gondii parasites by heterologous expression of a bacterial transporter protein. Mice infected with these transgenic parasites can now be cured from a lethal challenge with fosmidomycin. We propose that the varied extent of metabolite exchange between host and parasite is a crucial determinator of drug susceptibility and a predictor of future resistance.
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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.