Evidence map›Paper›PMID 12183226›Full record

ArticleAntimicrobial agents and chemotherapy2002

Oxidative stress increases susceptibility of Mycobacterium tuberculosis to isoniazid.

Vanja M Bulatovic, Nancy L Wengenack, James R Uhl, Leslie Hall, Glenn D Roberts, Franklin R Cockerill, Frank Rusnak

Open access · greenAbstract read
In one paragraph

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 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

17 citing papers in PubMed, 54 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Drug Discovery forInternational journal of molecular sciences · 2021
    Review
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  8. Sublethal Paraquat Confers Multidrug Tolerance inFrontiers in microbiology · 2020
    Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
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  15. Review
  16. Article
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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 1 institution in 1 country.

Vanja M BulatovicSection of Hematology Research and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Nancy L Wengenack
James R Uhl
Leslie Hall
Glenn D Roberts
Franklin R Cockerill
Frank Rusnak
Mayo Clinic · US

Funding

KatG Peroxidase in Isoniazid Activation and ResistanceR01AI047142 · NIAID · MAYO CLINIC COLL OF MEDICINE, ROCHESTER · PI OWEN, WHYTE G · 2002 to 2003
$468k
KATG PEROXIDASE IN ISONIAZID ACTIVATION AND RESISTANCER21AI047142 · NIAID · MAYO CLINIC COLL OF MEDICINE, ROCHESTER · PI OWEN, WHYTE G · 2001 to 2001
$250k
NIAID NIH HHS AI47142NIAID NIH HHS R01 AI047142NIAID NIH HHS R21 AI047142
6 · The paper itself

Abstract

Isoniazid is a first-line antibiotic used in the treatment of infections caused by Mycobacterium tuberculosis. Isoniazid is a prodrug requiring oxidative activation by the catalase-peroxidase hemoprotein, KatG. Resistance to isoniazid can be obtained by point mutations in the katG gene, with one of the most common being a threonine-for-serine substitution at position 315 (S315T). The S315T mutation is found in more than 50% of isoniazid-resistant clinical isolates and results in an approximately 200-fold increase in the MIC of isoniazid compared to that for M. tuberculosis H37Rv. In the present study we investigated the hypothesis that superoxide plays a role in KatG-mediated isoniazid activation. Plumbagin and clofazimine, compounds capable of generating superoxide anion, resulted in a lower MIC of isoniazid for M. tuberculosis H37Rv and a strain carrying the S315T mutation. These agents did not cause as great of an increase in isoniazid susceptibility in the mutant strain when the susceptibilities were assessed by using the inhibitory concentration that causes a 50% decrease in growth. These results provide evidence that superoxide can play a role in isoniazid activation. Since clofazimine alone has antitubercular activity, the observation of synergism between clofazimine and isoniazid raises the interesting possibility of using both drugs in combination to treat M. tuberculosis infections.

Indexed as

Bacterial ProteinsAntitubercular AgentsBase SequenceClofazimineDNA, BacterialDrug Resistance, MicrobialIsoniazidMicrobial Sensitivity TestsMolecular Sequence DataMycobacterium tuberculosisNaphthoquinonesOxidantsOxidative StressPeroxidasesSuperoxidesAntitubercular AgentsBacterial Proteinscatalase HPIClofazimineDNA, BacterialIsoniazidNaphthoquinonesOxidantsPeroxidasesplumbaginSuperoxides

Identifiers

PMID12183226
PMCPMC127408
OpenAlexW2133723544

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.