Evidence map›Paper›PMID 17158936›Full record

ArticleAntimicrobial agents and chemotherapy2007

Antiparasitic drug nitazoxanide inhibits the pyruvate oxidoreductases of Helicobacter pylori, selected anaerobic bacteria and parasites, and Campylobacter jejuni.

Paul S Hoffman, Gary Sisson, Matthew A Croxen, Kevin Welch, W Dean Harman, Nunilo Cremades, Michael G Morash

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed, 1 pooled it
8.5field-weighted citation impact, top 2% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

113 citing papers in PubMed, 1 synthesis or guideline pooled it, 240 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Evaluating the efficacy of nitazoxanide in uncomplicated amebic liver abscess.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2021
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  19. Journal of bacteriology · 2024
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53 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 3 countries.

Paul S HoffmanDivision of Infectious Diseases and International Health, 409 Lane Road, University of Virginia Health Systems, Charlottesville, VA 22908-1340, USA. psh2n@virginia.edu
Gary Sisson
Matthew A Croxen
Kevin Welch
W Dean Harman
Nunilo Cremades
Michael G Morash
University of Virginia · USDalhousie University · CAOffice of Infectious Diseases · USUniversidad de Zaragoza · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nitazoxanide (NTZ) exhibits broad-spectrum activity against anaerobic bacteria and parasites and the ulcer-causing pathogen Helicobacter pylori. Here we show that NTZ is a noncompetitive inhibitor (K(i), 2 to 10 microM) of the pyruvate:ferredoxin/flavodoxin oxidoreductases (PFORs) of Trichomonas vaginalis, Entamoeba histolytica, Giardia intestinalis, Clostridium difficile, Clostridium perfringens, H. pylori, and Campylobacter jejuni and is weakly active against the pyruvate dehydrogenase of Escherichia coli. To further mechanistic studies, the PFOR operon of H. pylori was cloned and overexpressed in E. coli, and the multisubunit complex was purified by ion-exchange chromatography. Pyruvate-dependent PFOR activity with NTZ, as measured by a decrease in absorbance at 418 nm (spectral shift from 418 to 351 nm), unlike the reduction of viologen dyes, did not result in the accumulation of products (acetyl coenzyme A and CO(2)) and pyruvate was not consumed in the reaction. NTZ did not displace the thiamine pyrophosphate (TPP) cofactor of PFOR, and the 351-nm absorbing form of NTZ was inactive. Optical scans and (1)H nuclear magnetic resonance analyses determined that the spectral shift (A(418) to A(351)) of NTZ was due to protonation of the anion (NTZ(-)) of the 2-amino group of the thiazole ring which could be generated with the pure compound under acidic solutions (pK(a) = 6.18). We propose that NTZ(-) intercepts PFOR at an early step in the formation of the lactyl-TPP transition intermediate, resulting in the reversal of pyruvate binding prior to decarboxylation and in coordination with proton transfer to NTZ. Thus, NTZ might be the first example of an antimicrobial that targets the "activated cofactor" of an enzymatic reaction rather than its substrate or catalytic sites, a novel mechanism that may escape mutation-based drug resistance.

Indexed as

Enzyme InhibitorsAcetyl Coenzyme AAnimalsAntiprotozoal AgentsBacteria, AnaerobicCampylobacter jejuniCarbon DioxideCloning, MolecularClostridiumCulture MediaHelicobacter pyloriKineticsL-Lactate DehydrogenaseMagnetic Resonance SpectroscopyNitro CompoundsParasitesAcetyl Coenzyme AAntiprotozoal AgentsCarbon DioxideCulture MediaEnzyme InhibitorsL-Lactate DehydrogenasenitazoxanideNitro CompoundsPyruvate Dehydrogenase ComplexPyruvic AcidThiamine PyrophosphateThiazoles

Identifiers

PMID17158936
PMCPMC1803158
OpenAlexW2160454557

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.