ReviewMicrobiology spectrum2014
Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis: Genes, Mutations, and Causalities.
Review in Microbiology spectrum, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 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
153 citing papers in PubMed, 1 synthesis or guideline pooled it, 276 citations in OpenAlex.
- Systematic Review of Mutations Associated with Isoniazid Resistance Points to Continuing Evolution and Subsequent Evasion of Molecular Detection, and Potential for Emergence of Multidrug Resistance in Clinical Strains of Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2021Pooled it
- Molecular Mechanisms Underlying Antimicrobial Resistance in Mycobacteria.International journal of molecular sciences · 2026Review
- Review
- Pharmacogenomics of antibacterial and antiviral therapies: Clinical actionability, evidence gaps, and future directions.Pharmacological reviews · 2026Review
- Covalent Inhibitors in Antimicrobial Drug Development-Beyond β-Lactams.Molecules (Basel, Switzerland) · 2026Review
- Growth arrest of Mycobacterium tuberculosis in acidic environments enhances their survival of antibiotic treatment.PLoS biology · 2026Article
- A cartridge-based assay for improved detection of multidrug-resistantJournal of clinical microbiology · 2026Article
- Host oxidative stress primes mycobacteria for rapid antibiotic resistance evolution.Nature communications · 2026Article
- Convolutional neural networks quantify antibiotic resistance in Mycobacterium tuberculosis with diagnostic grade accuracy and predict treatment response.Nature communications · 2026Article
- Predicting isoniazid resistance inJournal of clinical microbiology · 2026Article
- Discovery of pyridomycin derivatives as InhA inhibitors from actinomycetes through molecular networking and an In-House tandem mass library.Natural products and bioprospecting · 2026Article
- TheMicrobiology spectrum · 2026Article
- A Comprehensive Review of Genetic Mechanisms ofInfection and drug resistance · 2026Review
- From mutation detection to treatment decisions: CRISPR-enabled diagnostics for drug-resistant tuberculosis.Frontiers in bioengineering and biotechnology · 2026Review
- Inactivation of cAMP receptor protein (MSMEG_6189) increases isoniazid susceptibility inJournal of bacteriology · 2025Article
- Host oxidative stress primes mycobacteria for rapid antibiotic resistance evolution.Research square · 2025Article
- Detection of rifampin-resistant Mycobacterium tuberculosis using CRISPR/Cas14a-enabled molecular techniques.BMC infectious diseases · 2025Article
- A Multiplexed, Target-Based Phenotypic Screening Platform Using CRISPR Interference inACS infectious diseases · 2025Article
- Targeting Mycolic Acid Biosynthesis with Cyclic Sulfamates: A New Strategy againstACS infectious diseases · 2025Article
- Review
93 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 2 institutions in 1 country.
Funding
Abstract
Isoniazid (INH) is the cornerstone of tuberculosis (TB) chemotherapy, used for both treatment and prophylaxis of TB. The antimycobacterial activity of INH was discovered in 1952, and almost as soon as its activity was published, the first INH-resistant Mycobacterium tuberculosis strains were reported. INH and its structural analog and second-line anti-TB drug ethionamide (ETH) are pro-drugs. INH is activated by the catalase-peroxidase KatG, while ETH is activated by the monooxygenase EthA. The resulting active species reacts with NAD+ to form an INH-NAD or ETH-NAD adduct, which inhibits the enoyl ACP reductase InhA, leading to mycolic acid biosynthesis inhibition and mycobacterial cell death. The major mechanism of INH resistance is mutation in katG, encoding the activator of INH. One specific KatG variant, S315T, is found in 94% of INH-resistant clinical isolates. The second mechanism of INH resistance is a mutation in the promoter region of inhA (c-15t), which results in inhA overexpression and leads to titration of the drug. Mutations in the inhA open reading frame and promoter region are also the major mechanism of resistance to ETH, found more often in ETH-resistant clinical isolates than mutations in the activator of ETH. Other mechanisms of resistance to INH and ETH include expression changes of the drugs' activators, redox alteration, drug inactivation, and efflux pump activation. In this article, we describe each known mechanism of resistance to INH and ETH and its importance in M. tuberculosis clinical isolates.
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.