ArticleJournal of bacteriology2014
Response to metronidazole and oxidative stress is mediated through homeostatic regulator HsrA (HP1043) in Helicobacter pylori.
Article in Journal of bacteriology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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
30 citing papers in PubMed, 46 citations in OpenAlex.
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- Challenges and Prospects for Eradication ofPathogens (Basel, Switzerland) · 2025Review
- Novel Drug-like HsrA Inhibitors Exhibit Potent Narrow-Spectrum Antimicrobial Activities againstInternational journal of molecular sciences · 2024Article
- Article
- Profiling of the Helicobacter pylori redox switch HP1021 regulon using a multi-omics approach.Nature communications · 2023Article
- Molecular Mechanisms of Antibiotic Resistance and Novel Treatment Strategies forTropical medicine and infectious disease · 2023Review
- Insights into the Orchestration of Gene Transcription Regulators inInternational journal of molecular sciences · 2022Review
- Automated extraction of genes associated with antibiotic resistance from the biomedical literature.Database : the journal of biological databases and curation · 2022Article
- Flavonoids-Rich Plant Extracts AgainstFrontiers in pharmacology · 2022Review
- Two-component regulatory systems inFrontiers in cellular and infection microbiology · 2022Review
- 1,4-Dihydropyridine as a Promising Scaffold for Novel Antimicrobials AgainstFrontiers in microbiology · 2022Article
- Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity.International journal of molecular sciences · 2021Review
- Fighting the Antibiotic Crisis: Flavonoids as Promising Antibacterial Drugs AgainstFrontiers in cellular and infection microbiology · 2021Review
- Helicobacter pylori treatment in the post-antibiotics era-searching for new drug targets.Applied microbiology and biotechnology · 2020Review
- Chromosomal Resistance to Metronidazole in Clostridioides difficile Can Be Mediated by Epistasis between Iron Homeostasis and Oxidoreductases.Antimicrobial agents and chemotherapy · 2020Article
- Flavodoxins as Novel Therapeutic Targets againstInternational journal of molecular sciences · 2020Review
- Amixicile: A Concept Therapeutic for Treatment of Chronic Anaerobic Infections.British journal of gastroenterology · 2020Article
- Repurposing Dihydropyridines for Treatment ofPharmaceutics · 2019Article
- Chaperone activity of serine protease HtrA of Helicobacter pylori as a crucial survival factor under stress conditions.Cell communication and signaling : CCS · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Metronidazole (MTZ) is often used in combination therapies to treat infections caused by the gastric pathogen Helicobacter pylori. Resistance to MTZ results from loss-of-function mutations in genes encoding RdxA and FrxA nitroreductases. MTZ-resistant strains, when cultured at sub-MICs of MTZ (5 to 20 μg/ml), show dose-dependent defects in bacterial growth; depressed activities of many Krebs cycle enzymes, including pyruvate:ferredoxin oxidoreductase (PFOR); and low transcript levels of porGDAB (primer extension), phenotypes consistent with an involvement of a transcriptional regulator. Using a combination of protein purification steps, electrophoretic mobility shift assays (EMSAs), and mass spectrometry analyses of proteins bound to porG promoter sequences, we identified HP1043, an essential homeostatic global regulator (HsrA [for homeostatic stress regulator]). Competition EMSAs and supershift analyses with HsrA-enriched protein fractions confirmed specific binding to porGDAB and hsrA promoter sequences. Exposure to MTZ resulted in >10-fold decreases in levels of HsrA and in levels of the HsrA-regulated gene products PFOR and TlpB. Exposure to paraquat (PQ), hydrogen peroxide, or organic peroxides showed near equivalence with MTZ, revealing a common oxidative stress response pathway. Finally, direct superoxide dismutase (SOD) assays showed an inverse relationship between HsrA levels and SOD activity, suggesting that HsrA may serve as a repressor of sodB. As a homeostatic sentinel, HsrA appears to be ideally positioned to enable rapid shutdown of genes associated with metabolism and growth while activating (directly or indirectly) oxidative defense genes in response to low levels of toxic metabolites (MTZ or oxygen) before they reach DNA-damaging levels.
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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.