ArticleThe Journal of biological chemistry2011
Reduction of clofazimine by mycobacterial type 2 NADH:quinone oxidoreductase: a pathway for the generation of bactericidal levels of reactive oxygen species.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 3 of them syntheses that pooled it.
What it found
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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
178 citing papers in PubMed, 3 syntheses or guidelines pooled it, 332 citations in OpenAlex.
- Bedaquiline for treatment of non-tuberculous mycobacteria (NTM): a systematic review and meta-analysis.The Journal of antimicrobial chemotherapy · 2024Pooled it
- Systematic review of mutations associated with resistance to the new and repurposed Mycobacterium tuberculosis drugs bedaquiline, clofazimine, linezolid, delamanid and pretomanid.The Journal of antimicrobial chemotherapy · 2020Pooled it
- Systematic review of clofazimine for the treatment of drug-resistant tuberculosis.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2013Pooled it
- A 3-month clofazimine-rifapentine-containing regimen for drug-susceptible tuberculosis versus standard of care (Clo-Fast): a randomised, open-label, phase 2c clinical trial.The Lancet. Infectious diseases · 2026Trial
- A four‑gene signature identifies TKI‑induced persister cells and uncovers a ZLN005‑induced pyroptotic vulnerability via the GSDME pathway in EGFR‑mutant lung cancer.Molecular medicine reports · 2026Article
- Dual inhibition of respiratory complexes inMicrobiology spectrum · 2026Article
- Selective inhibition of respiratory complex I reveals a bioenergetic vulnerability inbioRxiv : the preprint server for biology · 2026Article
- Genomic heterogeneity of NAD(P)H dehydrogenase predisposes Cryptosporidium to clofazimine resistance.Nature microbiology · 2026Article
- Combination strategies targeting multiple ETC subunits as a rational approach for drug-resistant TB therapy.Archives of microbiology · 2026Review
- Pharmacokinetics of Inhaled Clofazimine Dry Powder in Healthy Mice.AAPS PharmSciTech · 2026Article
- QcrB inhibitor Q203 (Telacebec) can synergize with clofazimine and clarithromycin to control a Mycobacterium avium infection.PloS one · 2026Article
- A Comprehensive Review of Genetic Mechanisms ofInfection and drug resistance · 2026Review
- Remission spectroscopy resolves the mechanism of action of bedaquiline within living mycobacteria.Nature communications · 2025Article
- Advanced Nanosystems and Emerging Therapies: Innovations in Tuberculosis Treatment and Drug Resistance.Pharmaceutics · 2025Review
- Reference-based chemical-genetic interaction profiling to elucidate small molecule mechanism of action in Mycobacterium tuberculosis.Nature communications · 2025Article
- Examination of Genetic Mutations of Clofazimine Resistance in Drug-Resistant Mycobacterium TB Isolates.Current microbiology · 2025Article
- Widespread genomic heterogeneity at the type II NAD(P)H dehydrogenase locus predisposesbioRxiv : the preprint server for biology · 2025Article
- The acetyltransferase CysE modulates virulence and drug resistance of Mycobacterium tuberculosis by interfering with oxidative stress responses.Communications biology · 2025Article
- Microbiological evidence for the trisubstituted benzimidazoles targeting MmpL3 inAntimicrobial agents and chemotherapy · 2025Article
- Assessment of TB47 as a potential novel therapeutic agent:Antimicrobial agents and chemotherapy · 2025Article
118 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The mechanism of action of clofazimine (CFZ), an antimycobacterial drug with a long history, is not well understood. The present study describes a redox cycling pathway that involves the enzymatic reduction of CFZ by NDH-2, the primary respiratory chain NADH:quinone oxidoreductase of mycobacteria and nonenzymatic oxidation of reduced CFZ by O(2) yielding CFZ and reactive oxygen species (ROS). This pathway was demonstrated using isolated membranes and purified recombinant NDH-2. The reduction and oxidation of CFZ was measured spectrally, and the production of ROS was measured using a coupled assay system with Amplex Red. Supporting the ROS-based killing mechanism, bacteria grown in the presence of antioxidants are more resistant to CFZ. CFZ-mediated increase in NADH oxidation and ROS production were not observed in membranes from three different Gram-negative bacteria but was observed in Staphylococcus aureus and Saccharomyces cerevisiae, which is consistent with the known antimicrobial specificity of CFZ. A more soluble analog of CFZ, KS6, was synthesized and was shown to have the same activities as CFZ. These studies describe a pathway for a continuous and high rate of reactive oxygen species production in Mycobacterium smegmatis treated with CFZ and a CFZ analog as well as evidence that cell death produced by these agents are related to the production of these radical species.
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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.