ArticleAntimicrobial agents and chemotherapy2009
Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (nitroimidazole reductases).
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- A systematic review of the literature on mechanisms of 5-nitroimidazole resistance inParasitology · 2020Pooled it
- Metronidazole Activation by a Deeply Entangled Dimeric Malic Enzyme inPathogens (Basel, Switzerland) · 2025Article
- Roles of efflux pumps and nitroreductases in metronidazole-resistant Trichomonas vaginalis.Parasitology research · 2025Article
- Antimicrobial Resistance in Curable Sexually Transmitted Infections.Current HIV/AIDS reports · 2025Review
- High frequency of point mutations in the nitroreductase 4 and 6 genes of Trichomonas vaginalis associated with metronidazole resistance.Folia parasitologica · 2024Article
- Article
- Antigiardial and antiamebic activities of fexinidazole and its metabolites: new drug leads for giardiasis and amebiasis.Antimicrobial agents and chemotherapy · 2024Article
- Identification ofPathogens (Basel, Switzerland) · 2023Article
- Drug resistance patterns and genotype associations ofFrontiers in veterinary science · 2023Article
- Pyridyl Methylsulfinyl Benzimidazole Derivatives as Promising Agents againstMolecules (Basel, Switzerland) · 2022Article
- Recent advances in the molecular biology of the protist parasiteFaculty reviews · 2021Review
- Click chemistry-facilitated comprehensive identification of proteins adducted by antimicrobial 5-nitroimidazoles for discovery of alternative drug targets against giardiasis.PLoS neglected tropical diseases · 2020Article
- Development of a Novel Ex-vivo 3D Model to Screen Amoebicidal Activity on Infected Tissue.Scientific reports · 2019Article
- Nongenotoxic 3-Nitroimidazo[1,2-ACS medicinal chemistry letters · 2019Article
- Article
- An Efficient One-Pot Catalyzed Synthesis of 2,4-Disubstituted 5-Nitroimidazoles Displaying Antiparasitic and Antibacterial Activities.Molecules (Basel, Switzerland) · 2017Article
- Mechanism-Informed Refinement Reveals Altered Substrate-Binding Mode for Catalytically Competent Nitroreductase.Structure (London, England : 1993) · 2017Article
- Identification of a type I nitroreductase gene in non-virulent Trypanosoma rangeli.Memorias do Instituto Oswaldo Cruz · 2017Article
- Click Chemistry-Facilitated Structural Diversification of Nitrothiazoles, Nitrofurans, and Nitropyrroles Enhances Antimicrobial Activity against Giardia lamblia.Antimicrobial agents and chemotherapy · 2017Article
- Genetic Indicators of Drug Resistance in the Highly Repetitive Genome of Trichomonas vaginalis.Genome biology and evolution · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Infections with Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis, which cause diarrhea, dysentery, and vaginitis, respectively, are each treated with metronidazole. Here we show that Giardia, Entamoeba, and Trichomonas have oxygen-insensitive nitroreductase (ntr) genes which are homologous to those genes that have nonsense mutations in metronidazole-resistant Helicobacter pylori isolates. Entamoeba and Trichomonas also have nim genes which are homologous to those genes expressed in metronidazole-resistant Bacteroides fragilis isolates. Recombinant Giardia, Entamoeba, and Trichomonas nitroreductases used NADH rather than the NADPH used by Helicobacter, and two recombinant Entamoeba nitroreductases increased the metronidazole sensitivity of transformed Escherichia coli strains. Conversely, the recombinant nitroimidazole reductases (NIMs) of Entamoeba and Trichmonas conferred very strong metronidazole resistance to transformed bacteria. The Ehntr1 gene of the genome project HM-1:IMSS strain of Entamoeba histolytica had a nonsense mutation, and the same nonsense mutation was present in 3 of 22 clinical isolates of Entamoeba. While ntr and nim mRNAs were variably expressed by cultured Entamoeba and Trichomonas isolates, there was no relationship to metronidazole sensitivity. We conclude that microaerophilic protists have bacterium-like enzymes capable of activating metronidazole (nitroreductases) and inactivating metronidazole (NIMs). While Entamoeba and Trichomonas displayed some of the changes (nonsense mutations and gene overexpression) associated with metronidazole resistance in bacteria, these changes did not confer metronidazole resistance to the microaerophilic protists examined here.
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