ReviewJournal of molecular biology2019
The Isoniazid Paradigm of Killing, Resistance, and Persistence in Mycobacterium tuberculosis.
Review in Journal of molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 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
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- The mycobacterial ATP burst is a lysis artifact and serves as an assay for drug-induced cell wall damage.Cell reports · 2026Article
- Targeting cGAS-STING signaling to overcome antibiotic-resistant bacterial infections: Challenges and opportunities.Science advances · 2026Review
- Host oxidative stress primes mycobacteria for rapid antibiotic resistance evolution.Nature communications · 2026Article
- Reappraising TB preventive treatment in India: programmatic and ethical implications of subclinical tuberculosis in household contacts.The Lancet regional health. Southeast Asia · 2026Review
- Exploring the partial immunological mechanisms of hepatitis B virus reactivation in patients with hepatitis B and tuberculosis.Frontiers in cellular and infection microbiology · 2026Article
- Investigation of Potent Anti-Drug design, development and therapy · 2026Article
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- The Biosynthetic Pathway of Mycolic Acids: Dual-Function Targets for Tuberculosis Therapeutics and Green Steroid Drugs Biomanufacturing.Pharmaceutics · 2025Review
- Vitamin BCommunications biology · 2025Article
- Host oxidative stress primes mycobacteria for rapid antibiotic resistance evolution.Research square · 2025Article
- The mycobacterial ATP burst is a lysis artifact and serves as an assay for drug-induced cell wall damage.bioRxiv : the preprint server for biology · 2025Article
- The pH gradient contributes to persistence in Mycobacterium tuberculosis.Research square · 2025Article
- Isoniazid-rhodanine molecular hybrids: design, synthesis, antimycobacterial activity and computational validation.RSC advances · 2025Article
- Bactericidal activity of gallic acid against multidrug-resistant Mycobacterium tuberculosis.Archives of microbiology · 2025Article
- Netupitant Exhibits Potent Activity onACS infectious diseases · 2025Article
- Homoleptic complexes of titanium(iv) fused with O^N^O Schiff base derivatives: design, BSA-DNA interaction, molecular docking, DFT and cytotoxicity.RSC advances · 2025Article
22 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
Abstract
Isoniazid (INH) was the first synthesized drug that mediated bactericidal killing of the bacterium Mycobacterium tuberculosis, a major clinical breakthrough. To this day, INH remains a cornerstone of modern tuberculosis (TB) chemotherapy. This review describes the serendipitous discovery of INH, its effectiveness on TB patients, and early studies to discover its mechanisms of bacteriocidal activity. Forty years after its introduction as a TB drug, the development of gene transfer in mycobacteria enabled the discovery of the genes encoding INH resistance, namely, the activator (katG) and the target (inhA) of INH. Further biochemical and x-ray crystallography studies on KatG and InhA proteins and mutants provided comprehensive understanding of INH mode of action and resistance mechanisms. Bacterial cultures can harbor subpopulations that are genetically or phenotypically resistant cells, the latter known as persisters. Treatment of exponentially growing cultures of M. tuberculosis with INH reproducibly kills 99% to 99.9% of cells in 3 days. Importantly, the surviving cells are slowly replicating or non-replicating cells expressing a unique stress response signature: these are the persisters. These persisters can be visualized using dual-reporter mycobacteriophages and their formation prevented using reducing compounds, such as N-acetylcysteine or vitamin C, that enhance M. tuberculosis' respiration. Altogether, this review portrays a detailed molecular analysis of INH killing and resistance mechanisms including persistence. The phenomenon of persistence is clearly the single greatest impediment to TB control, and research aimed at understanding persistence will provide new strategies to improve TB chemotherapy.
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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.