ArticleAntimicrobial agents and chemotherapy2015
Resistance to the antimicrobial agent fosmidomycin and an FR900098 prodrug through mutations in the deoxyxylulose phosphate reductoisomerase gene (dxr).
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Fosmidomycin for the Treatment of Canine Otitis Externa: A Randomised, Double-Blinded, Controlled 'Split Body' Clinical Trial.Veterinary dermatology · 2026Article
- In vitro activity of the antimalarial, antibiotic drugs fosmidomycin and clindamycin against clinical isolates of bacterial bloodstream infections in febrile, hospitalized Ghanaian children.Malaria journal · 2026Article
- Prodrug activation in malaria parasites mediated by an imported erythrocyte esterase, acylpeptide hydrolase (APEH).Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Aptamers as innovative tools for malaria diagnosis and treatment: advances and future perspectives.Biology methods & protocols · 2025Review
- Prodrug activation in malaria parasites mediated by an imported erythrocyte esterase, acylpeptide hydrolase (APEH).bioRxiv : the preprint server for biology · 2024Article
- Article
- Over 40 Years of Fosmidomycin Drug Research: A Comprehensive Review and Future Opportunities.Pharmaceuticals (Basel, Switzerland) · 2022Review
- GAPDH mediates drug resistance and metabolism in Plasmodium falciparum malaria parasites.PLoS pathogens · 2022Article
- High-Throughput Screen for Inhibitors ofACS omega · 2022Article
- Drug Repurposing: A Review of Old and New Antibiotics for the Treatment of Malaria: Identifying Antibiotics with a Fast Onset of Antiplasmodial Action.Molecules (Basel, Switzerland) · 2021Review
- Multipurpose Drugs Active Against BothFrontiers in cellular and infection microbiology · 2021Review
- Antimicrobial Prodrug Activation by the Staphylococcal Glyoxalase GloB.ACS infectious diseases · 2020Article
- Article
- Potent, specific MEPicides for treatment of zoonotic staphylococci.PLoS pathogens · 2020Article
- Predicting Drug Resistance Using Deep Mutational Scanning.Molecules (Basel, Switzerland) · 2020Review
- Inhibition of theACS omega · 2020Article
- Prenylquinones in Human Parasitic Protozoa: Biosynthesis, Physiological Functions, and Potential as Chemotherapeutic Targets.Molecules (Basel, Switzerland) · 2019Review
- A computational study of the molecular basis of antibiotic resistance in a DXR mutant.Journal of computer-aided molecular design · 2019Article
- An Artificial Pathway for Isoprenoid Biosynthesis Decoupled from Native Hemiterpene Metabolism.ACS synthetic biology · 2019Article
- Genomic Deoxyxylulose Phosphate Reductoisomerase (DXR) Mutations Conferring Resistance to the Antimalarial Drug Fosmidomycin in E. coli.ACS synthetic biology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
There is a pressing need for new antimicrobial therapies to combat globally important drug-resistant human pathogens, including Plasmodium falciparum malarial parasites, Mycobacterium tuberculosis, and Gram-negative bacteria, including Escherichia coli. These organisms all possess the essential methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, which is not found in humans. The first dedicated enzyme of the MEP pathway, 1-deoxy-d-xylulose 5-phosphate reductoisomerase (Dxr), is inhibited by the phosphonic acid antibiotic fosmidomycin and its analogs, including the N-acetyl analog FR900098 and the phosphoryl analog fosfoxacin. In order to identify mutations in dxr that confer resistance to these drugs, a library of E. coli dxr mutants was screened at lethal fosmidomycin doses. The most resistant allele (with the S222T mutation) alters the fosmidomycin-binding site of Dxr. The expression of this resistant allele increases bacterial resistance to fosmidomycin and other fosmidomycin analogs by 10-fold. These observations confirm that the primary cellular target of fosmidomycin is Dxr. Furthermore, cell lines expressing Dxr-S222T will be a powerful tool to confirm the mechanisms of action of future fosmidomycin analogs.
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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.