ArticleAntimicrobial agents and chemotherapy2005
Alternative pathway of metronidazole activation in Trichomonas vaginalis hydrogenosomes.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- A systematic review of the literature on mechanisms of 5-nitroimidazole resistance inParasitology · 2020Pooled it
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- Metronidazole Activation by a Deeply Entangled Dimeric Malic Enzyme inPathogens (Basel, Switzerland) · 2025Article
- Functions of nitroreductases in mycobacterial physiology and drug susceptibility.Journal of bacteriology · 2025Review
- Targeting histone acetylation to overcome drug resistance in the parasitebioRxiv : the preprint server for biology · 2025Article
- Imidazole Carbamates as a Promising Alternative for Treating Trichomoniasis: In Vitro Effects on the Growth and Gene Expression ofMolecules (Basel, Switzerland) · 2024Article
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- Identification ofPathogens (Basel, Switzerland) · 2023Article
- Unusual Cell Structures and Organelles inMicroorganisms · 2022Review
- Gold(I) Phosphine Derivatives with Improved Selectivity as Topically Active Drug Leads to Overcome 5-Nitroheterocyclic Drug Resistance inJournal of medicinal chemistry · 2021Article
- An Efficient One-Pot Catalyzed Synthesis of 2,4-Disubstituted 5-Nitroimidazoles Displaying Antiparasitic and Antibacterial Activities.Molecules (Basel, Switzerland) · 2017Article
- Novel functions of an iron-sulfur flavoprotein from Trichomonas vaginalis hydrogenosomes.Antimicrobial agents and chemotherapy · 2014Article
- Hydrogenosome metabolism is the key target for antiparasitic activity of resveratrol against Trichomonas vaginalis.Antimicrobial agents and chemotherapy · 2013Article
- Getting trichy: tools and approaches to interrogating Trichomonas vaginalis in a post-genome world.Trends in parasitology · 2013Review
- Biochemistry and evolution of anaerobic energy metabolism in eukaryotes.Microbiology and molecular biology reviews : MMBR · 2012Review
- A machine learning approach to identify hydrogenosomal proteins in Trichomonas vaginalis.Eukaryotic cell · 2012Article
- Trichomonas vaginalis: treatment questions and challenges.Expert review of anti-infective therapy · 2012Article
- Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation.Antimicrobial agents and chemotherapy · 2012Article
- Pyruvate:ferredoxin oxidoreductase and thioredoxin reductase are involved in 5-nitroimidazole activation while flavin metabolism is linked to 5-nitroimidazole resistance in Giardia lamblia.The Journal of antimicrobial chemotherapy · 2011Article
- Evolution of Tumor Metabolism might Reflect Carcinogenesis as a Reverse Evolution process (Dismantling of Multicellularity).Cancers · 2011Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metronidazole and related 5-nitroimidazoles are the only available drugs in the treatment of human urogenital trichomoniasis caused by the protozoan parasite Trichomonas vaginalis. The drugs are activated to cytotoxic anion radicals by their reduction within the hydrogenosomes. It has been established that electrons required for metronidazole activation are released from pyruvate by the activity of pyruvate:ferredoxin oxidoreductase and transferred to the drug by a low-redox-potential carrier, ferredoxin. Here we describe a novel pathway involved in the drug activation within the hydrogenosome. The source of electrons is malate, another major hydrogenosomal substrate, which is oxidatively decarboxylated to pyruvate and CO2 by NAD-dependent malic enzyme. The electrons released during this reaction are transferred from NADH to ferredoxin by NADH dehydrogenase homologous to the catalytic module of mitochondrial complex I, which uses ferredoxin as electron acceptor. Trichomonads acquire high-level metronidazole resistance only after both pyruvate- and malate-dependent pathways of metronidazole activation are eliminated from the hydrogenosomes.
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