ArticleAntimicrobial agents and chemotherapy2011
Impaired parasite attachment as fitness cost of metronidazole resistance in Giardia lamblia.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- 5-Nitrothiazol-Clofibric Acid Analogs as Potent Agents Against Nitazoxanide-ResistantMolecules (Basel, Switzerland) · 2026Article
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- Genotype-Specific Small EVs Released by Giardia lamblia Act as Mediators of Phenotypic Adaptation Under Metronidazole-Induced Stress.Journal of extracellular vesicles · 2025Article
- Tetramerization of deoxyadenosine kinase meets the demands of a DNA replication substrate challenge in Giardia intestinalis.Nucleic acids research · 2024Article
- Antigiardial and antiamebic activities of fexinidazole and its metabolites: new drug leads for giardiasis and amebiasis.Antimicrobial agents and chemotherapy · 2024Article
- Fused Enzyme Glucose-6-Phosphate Dehydrogenase::6-Phosphogluconolactonase (G6PD::6PGL) as a Potential Drug Target inMicroorganisms · 2024Review
- Giardia duodenalis: Flavohemoglobin is involved in drug biotransformation and resistance to albendazole.PLoS pathogens · 2022Article
- Giardia intestinalis thymidine kinase is a high-affinity enzyme crucial for DNA synthesis and an exploitable target for drug discovery.The Journal of biological chemistry · 2022Article
- Characterization of Metronidazole-ResistantFrontiers in microbiology · 2022Article
- Review
- Review
- Giardia duodenalis Virulence - "To Be, or Not To Be".Current tropical medicine reports · 2021Review
- Discovery and Preclinical Development of Antigiardiasis Fumagillol Derivatives.Antimicrobial agents and chemotherapy · 2020Article
- 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
- Ascorbic acid potentiates the Giardia duodenalis growth inhibitory activity of pure Terminalia ferdinandiana Exell compounds.Parasitology research · 2020Article
- On the molecular and cellular effects of omeprazole to further support its effectiveness as an antigiardial drug.Scientific reports · 2019Article
- Genetic variation in metronidazole metabolism and oxidative stress pathways in clinicalInfection and drug resistance · 2019Article
- Differential protein expression and post-translational modifications in metronidazole-resistant Giardia duodenalis.GigaScience · 2018Article
- Treatment-refractory giardiasis: challenges and solutions.Infection and drug resistance · 2018Review
- Click Chemistry-Facilitated Structural Diversification of Nitrothiazoles, Nitrofurans, and Nitropyrroles Enhances Antimicrobial Activity against Giardia lamblia.Antimicrobial agents and chemotherapy · 2017Article
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9 authors.
Funding
Abstract
Infections with the diarrheagenic protozoan pathogen Giardia lamblia are most commonly treated with metronidazole (Mz). Treatment failures with Mz occur in 10 to 20% of cases and Mz resistance develops in the laboratory, yet clinically, Mz-resistant (Mz(r)) G. lamblia has rarely been isolated from patients. To understand why clinical Mz(r) isolates are rare, we questioned whether Mz resistance entails fitness costs to the parasite. Our studies employed several newly generated and established isogenic Mz(r) cell lines with stable, high-level resistance to Mz and significant cross-resistance to tinidazole, nitazoxanide, and furazolidone. Oral infection of suckling mice revealed that three of five Mz(r) cell lines could not establish infection, while two Mz(r) cell lines infected pups, albeit with reduced efficiencies. Failure to colonize resulted from a diminished capacity of the parasite to attach to the intestinal mucosa in vivo and to epithelial cells and plastic surfaces in vitro. The attachment defect was related to impaired glucose metabolism, since the noninfectious Mz(r) lines consumed less glucose, and glucose promoted ATP-independent parasite attachment in the parental lines. Thus, resistance of Giardia to Mz is accompanied by a glucose metabolism-related attachment defect that can interfere with colonization of the host. Because glucose-metabolizing pathways are important for activation of the prodrug Mz, it follows that a fitness trade-off exists between diminished Mz activation and reduced infectivity, which may explain the observed paucity of clinical Mz(r) isolates of Giardia. However, the data also caution that some forms of Mz resistance do not markedly interfere with in vivo infectivity.
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