ArticleAntimicrobial agents and chemotherapy2002
Enzymes associated with reductive activation and action of nitazoxanide, nitrofurans, and metronidazole in Helicobacter pylori.
Article in Antimicrobial agents and chemotherapy, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
- A review and meta-analysis of the impact of intestinal worms on child growth and nutrition.Maternal & child nutrition · 2008Pooled it
- A randomized study comparing levofloxacin, omeprazole, nitazoxanide, and doxycycline versus triple therapy for the eradication of Helicobacter pylori.The American journal of gastroenterology · 2011Trial
- Nitazoxanide in treatment of Helicobacter pylori: a clinical and in vitro study.Antimicrobial agents and chemotherapy · 2003Trial
- Novel Prodrug Strategies for the Treatment of Tuberculosis.Chemistry, an Asian journal · 2024Review
- Pyridopyrimidinones as a new chemotype of calcium dependent protein kinase 1 (CDPK1) inhibitors for Cryptosporidium.Molecular and biochemical parasitology · 2024Article
- High frequency of point mutations in the nitroreductase 4 and 6 genes of Trichomonas vaginalis associated with metronidazole resistance.Folia parasitologica · 2024Article
- Introducing the NUATEI Consortium: A Mexican Research Program for the Identification of Natural and Synthetic Antimicrobial Compounds for Prevalent Infectious Diseases.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Anti-Cryptosporidial Drug-Discovery Challenges and Existing Therapeutic Avenues: A "One-Health" Concern.Life (Basel, Switzerland) · 2024Review
- New nitazoxanide derivatives: design, synthesis, biological evaluation, and molecular docking studies as antibacterial and antimycobacterial agents.RSC medicinal chemistry · 2023Article
- Standardization of an antiviral pipeline for human norovirus in human intestinal enteroids demonstrates nitazoxanide has no to weak antiviral activity.Antimicrobial agents and chemotherapy · 2023Article
- Nitazoxanide Inhibits the Bifunctional Enzyme GlG6PD::6PGL ofInternational journal of molecular sciences · 2023Article
- A Standardized Antiviral Pipeline for Human Norovirus in Human Intestinal Enteroids Demonstrates No Antiviral Activity of Nitazoxanide.bioRxiv : the preprint server for biology · 2023Article
- A case of septic shock due to delayed diagnosis of Cryptosporidium infection after liver transplantation.BMC infectious diseases · 2023Article
- Antibiotic resistance in Helicobacter pylori: From potential biomolecular mechanisms to clinical practice.Journal of clinical laboratory analysis · 2023Review
- Molecular Mechanisms of Antibiotic Resistance and Novel Treatment Strategies forTropical medicine and infectious disease · 2023Review
- Identification and Validation of a Novel Antibacterial Compound MZ-01 against Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2022Article
- Investigations of nitazoxanide molecular targets and pathways for the treatment of hepatocellular carcinoma using network pharmacology and molecular docking.Frontiers in pharmacology · 2022Article
- Addition of Nitazoxanide to Standard Clarithromycin Based Triple Therapy for 2 Weeks Effectively Eradicates Treatment-NaiveMiddle East journal of digestive diseases · 2022Article
- Helicobacter pylori infection and antibiotic resistance - from biology to clinical implications.Nature reviews. Gastroenterology & hepatology · 2021Review
- The Integrity of Heme Is Essential for Reproducible Detection of Metronidazole-Resistant Clostridioides difficile by Agar Dilution Susceptibility Tests.Journal of clinical microbiology · 2021Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Nitazoxanide (NTZ) is a redox-active nitrothiazolyl-salicylamide prodrug that kills Helicobacter pylori and also many anaerobic bacterial, protozoan, and helminthic species. Here we describe development and use of a spectrophotometric assay, based on nitroreduction of NTZ at 412 nm, to identify H. pylori enzymes responsible for its activation and mode of action. Three enzymes that reduce NTZ were identified: two related NADPH nitroreductases, which also mediate susceptibility to metronidazole (MTZ) (RdxA and FrxA), and pyruvate oxidoreductase (POR). Recombinant His-tagged RdxA, FrxA, and POR, overexpressed in nitroreductase-deficient Escherichia coli, each rapidly reduced NTZ, whereas only FrxA and to a lesser extent POR reduced nitrofuran substrates (furazolidone, nitrofurantoin, and nitrofurazone). POR exhibited no MTZ reductase activity either in extracts of H. pylori or following overexpression in E. coli; RdxA exhibited no nitrofuran reductase activity, and FrxA exhibited no MTZ reductase activity. Analysis of mutation to rifampin resistance (Rif(r)) indicated that NTZ was not mutagenic and that nitrofurans were only weakly mutagenic. Alkaline gel DNA electrophoresis indicated that none of these prodrugs caused DNA breakage. In contrast, MTZ caused DNA damage and was strongly mutagenic. We conclude that POR, an essential enzyme, is responsible for most or all of the bactericidal effects of NTZ against H. pylori. While loss-of-function mutations in rdxA and frxA produce a Mtz(r) phenotype, they do not contribute much to the innate susceptibility of H. pylori to NTZ or nitrofurans.
Indexed as
Identifiers
What OpenQuestion holds
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.