ArticleAntimicrobial agents and chemotherapy2015
Mode of Action of Clofazimine and Combination Therapy with Benzothiazinones against Mycobacterium tuberculosis.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 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
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.American journal of respiratory and critical care medicine · 2019Guideline
- Pathogenesis of Tuberculosis: Interplay Between Host Antituberculosis Immunity and Immune Evasion Strategies ofMedComm · 2026Review
- Genomic heterogeneity of NAD(P)H dehydrogenase predisposes Cryptosporidium to clofazimine resistance.Nature microbiology · 2026Article
- The Mycobacterium abscessus cytochrome bcc:aaNature communications · 2026Article
- Current and emerging therapies for pulmonary tuberculosis in adults.BMJ medicine · 2026Review
- 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
- TAK1 phosphorylation mediates macozinone (PBTZ169) induced innate immune activation against tuberculosis.mSphere · 2025Article
- Widespread genomic heterogeneity at the type II NAD(P)H dehydrogenase locus predisposesbioRxiv : the preprint server for biology · 2025Article
- Integration of multi-modal measurements identifies critical mechanisms of tuberculosis drug action.Cell systems · 2025Article
- Contribution of telacebec to novel drug regimens in a murine tuberculosis model.Antimicrobial agents and chemotherapy · 2025Article
- A scoping review about smoking, smoking cessation and their effects on anti-tuberculosis agents: insights into drug metabolisms, safety, and effectiveness.Frontiers in pharmacology · 2025Review
- Inhibitors of Type II NADH Dehydrogenase Enzyme: A Review.Current protein & peptide science · 2025Review
- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
- Randomized, Double-Blind, Placebo-Controlled Study of Anti-Mycobacterial Therapy (RHB-104) in Active Crohn's Disease.Antibiotics (Basel, Switzerland) · 2024Article
- Post-functionalization of triamino-phenazinium dyes to reach near-infrared emission.RSC advances · 2024Article
- Antitubercular drugs: possible role of natural products acting as antituberculosis medication in overcoming drug resistance and drug-induced hepatotoxicity.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Tackling Nontuberculous Mycobacteria by Repurposable Drugs and Potential Leads from Natural Products.Current topics in medicinal chemistry · 2024Review
- Micro-nanoemulsion and nanoparticle-assisted drug delivery against drug-resistant tuberculosis: recent developments.Clinical microbiology reviews · 2023Review
- TargetingRSC medicinal chemistry · 2023Review
9 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
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clofazimine (CZM) is an antileprosy drug that was recently repurposed for treatment of multidrug-resistant tuberculosis. In Mycobacterium tuberculosis, CZM appears to act as a prodrug, which is reduced by NADH dehydrogenase (NDH-2), to release reactive oxygen species upon reoxidation by O2. CZM presumably competes with menaquinone (MK-4), a key cofactor in the mycobacterial electron transfer chain, for its reduction by NDH-2. We studied the effect of MK-4 supplementation on the activity of CZM against M. tuberculosis and found direct competition between CZM and MK-4 for the cidal effect of CZM, against nonreplicating and actively growing bacteria, as MK-4 supplementation blocked the drug's activity against nonreplicating bacteria. We demonstrated that CZM, like bedaquiline, is synergistic in vitro with benzothiazinones such as 2-piperazino-benzothiazinone 169 (PBTZ169), and this synergy also occurs against nonreplicating bacteria. The synergy between CZM and PBTZ169 was lost in an MK-4-rich medium, indicating that MK-4 is the probable link between their activities. The efficacy of the dual combination of CZM and PBTZ169 was tested in vivo, where a great reduction in bacterial load was obtained in a murine model of chronic tuberculosis. Taken together, these data confirm the potential of CZM in association with PBTZ169 as the basis for a new regimen against drug-resistant strains of M. tuberculosis.
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.