ArticleThe Journal of antimicrobial chemotherapy2011
Pyruvate:ferredoxin oxidoreductase and thioredoxin reductase are involved in 5-nitroimidazole activation while flavin metabolism is linked to 5-nitroimidazole resistance in Giardia lamblia.
Article in The Journal of antimicrobial chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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.
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Who cites it
64 citing papers in PubMed, 130 citations in OpenAlex.
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- Proteomic Evidence for Biofilm-Mediated Copper Stress Adaptation in Oleidesulfovibrio alaskensis G20.Environmental microbiology · 2026Article
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- Vitamin D: a potential therapeutic for giardiasis in experimentally infected mice.Scientific reports · 2026Article
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- Viral load dependent cellular heterogeneity in Trichomonas vaginalis at the single cell level.iScience · 2026Article
- Genotype-Specific Small EVs Released by Giardia lamblia Act as Mediators of Phenotypic Adaptation Under Metronidazole-Induced Stress.Journal of extracellular vesicles · 2025Article
- Identification and characterization of archaeal-type FAD synthase as a novel tractable drug target from the parasitic protozoamSphere · 2024Article
- Killing tumor-associated bacteria with a liposomal antibiotic generates neoantigens that induce anti-tumor immune responses.Nature biotechnology · 2024Article
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- Fused Enzyme Glucose-6-Phosphate Dehydrogenase::6-Phosphogluconolactonase (G6PD::6PGL) as a Potential Drug Target inMicroorganisms · 2024Review
- Nitazoxanide Inhibits the Bifunctional Enzyme GlG6PD::6PGL ofInternational journal of molecular sciences · 2023Article
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- Ultrastructural Alterations of the Human PathogenPathogens (Basel, Switzerland) · 2023Review
- Mass Spectrometry-Based Metabolomics Revealed Effects of Metronidazole onPharmaceuticals (Basel, Switzerland) · 2023Article
- Pyridyl Methylsulfinyl Benzimidazole Derivatives as Promising Agents againstMolecules (Basel, Switzerland) · 2022Article
- An Overview of Mucosa-Associated Protozoa: Challenges in Chemotherapy and Future Perspectives.Frontiers in cellular and infection microbiology · 2022Review
- Characterization of Metronidazole-ResistantFrontiers in microbiology · 2022Article
- Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity.International journal of molecular sciences · 2021Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
objectivesThe mechanism of action of, and resistance to, metronidazole in the anaerobic (or micro-aerotolerant) protozoan parasite Giardia lamblia has long been associated with the reduction of ferredoxin (Fd) by the enzyme pyruvate:ferredoxin oxidoreductase (PFOR) and the subsequent activation of metronidazole by Fd to toxic radical species. Resistance to metronidazole has been associated with down-regulation of PFOR and Fd. The aim of this study was to determine whether the PFOR/Fd couple is the only pathway involved in metronidazole activation in Giardia.
methodsPFOR and Fd activities were measured in extracts of highly metronidazole-resistant (MTR(r)) lines and activities of recombinant G. lamblia thioredoxin reductase (GlTrxR) and NADPH oxidase were assessed for their involvement in metronidazole activation and resistance.
resultsWe demonstrated that several lines of highly MTR(r) G. lamblia have fully functional PFOR and Fd indicating that PFOR/Fd-independent mechanisms are involved in metronidazole activation and resistance in these cells. Flavin-dependent GlTrxR, like TrxR of other anaerobic protozoa, reduces 5-nitroimidazole compounds including metronidazole, although expression of TrxR is not decreased in MTR(r) Giardia. However, reduction of flavins is suppressed in highly MTR(r) cells, as evidenced by as much as an 80% decrease in NADPH oxidase flavin mononucleotide reduction activity. This suppression is consistent with generalized impaired flavin metabolism in highly MTR(r) Trichomonas vaginalis.
conclusionsThese data add to the mounting evidence against the dogma that PFOR/Fd is the only couple with a low enough redox potential to reduce metronidazole in anaerobes and point to the multi-factorial nature of metronidazole resistance.
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Registered trials
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