ArticleJournal of bacteriology2000
Inactivation of the inhA-encoded fatty acid synthase II (FASII) enoyl-acyl carrier protein reductase induces accumulation of the FASI end products and cell lysis of Mycobacterium smegmatis.
Article in Journal of bacteriology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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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.
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Who cites it
90 citing papers in PubMed, 278 citations in OpenAlex.
- Identifying potent inhibitors for Mycobacterium tuberculosis MabA (FabG1).Molecular diversity · 2026Article
- The Biosynthetic Pathway of Mycolic Acids: Dual-Function Targets for Tuberculosis Therapeutics and Green Steroid Drugs Biomanufacturing.Pharmaceutics · 2025Review
- Mycobacterium tuberculosis FAS-II pathway targeted integrative deep learning based identification of potential anti-tubercular agents.Journal of computer-aided molecular design · 2025Article
- Investigating the Mechanism of Antimycobacterial and Antiproliferative Activity of (E)-N'-Benzylidenepyrazine-2-Carbohydrazides and their Derivatives.ChemMedChem · 2025Article
- Metabolic rewiring of isoniazid sensitivity inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- The CRISPR-dCas9 interference system suppresses inhA gene expression in Mycobacterium smegmatis.Scientific reports · 2024Article
- Fluorogenic Probes of the Mycobacterial Membrane as Reporters of Antibiotic Action.Journal of the American Chemical Society · 2024Article
- Inducing vulnerability to InhA inhibition restores isoniazid susceptibility in drug-resistantmBio · 2024Article
- Molecular Mechanisms of MmpL3 Function and Inhibition.Microbial drug resistance (Larchmont, N.Y.) · 2023Review
- Polyphosphate kinase 1 is involved in formation, the morphology and ultramicrostructure of biofilm ofHeliyon · 2023Article
- Exploring the Antitubercular Activity of Anthranilic Acid Derivatives: From MabA (FabG1) Inhibition to Intrabacterial Acidification.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Genetic Characterization Conferred Co-Resistance to Isoniazid and Ethionamide inInfection and drug resistance · 2023Article
- Synthesis, Biological Evaluation and Computational Studies of New Hydrazide Derivatives Containing 1,3,4-Oxadiazole as Antitubercular Agents.International journal of molecular sciences · 2022Article
- Activation of the SigE-SigB signaling pathway by inhibition of the respiratory electron transport chain and its effect on rifampicin resistance in Mycobacterium smegmatis.Journal of microbiology (Seoul, Korea) · 2022Article
- Identification of Novel Inhibitor of Enoyl-Acyl Carrier Protein Reductase (InhA) Enzyme inAntibiotics (Basel, Switzerland) · 2022Article
- The mycobacterial desaturase DesA2 is associated with mycolic acid biosynthesis.Scientific reports · 2022Article
- Machine Learning Models forMolecular pharmaceutics · 2022Article
- Conventional and Microwave-Assisted Synthesis, Antitubercular Activity, and Molecular Docking Studies of Pyrazole and Oxadiazole Hybrids.ACS omega · 2021Article
- Biological and Biochemical Evaluation of Isatin-Isoniazid Hybrids as Bactericidal Candidates againstAntimicrobial agents and chemotherapy · 2021Article
30 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The mechanism of action of isoniazid (INH), a first-line antituberculosis drug, is complex, as mutations in at least five different genes (katG, inhA, ahpC, kasA, and ndh) have been found to correlate with isoniazid resistance. Despite this complexity, a preponderance of evidence implicates inhA, which codes for an enoyl-acyl carrier protein reductase of the fatty acid synthase II (FASII), as the primary target of INH. However, INH treatment of Mycobacterium tuberculosis causes the accumulation of hexacosanoic acid (C(26:0)), a result unexpected for the blocking of an enoyl-reductase. To test whether inactivation of InhA is identical to INH treatment of mycobacteria, we isolated a temperature-sensitive mutation in the inhA gene of Mycobacterium smegmatis that rendered InhA inactive at 42 degrees C. Thermal inactivation of InhA in M. smegmatis resulted in the inhibition of mycolic acid biosynthesis, a decrease in hexadecanoic acid (C(16:0)) and a concomitant increase of tetracosanoic acid (C(24:0)) in a manner equivalent to that seen in INH-treated cells. Similarly, INH treatment of Mycobacterium bovis BCG caused an inhibition of mycolic acid biosynthesis, a decrease in C(16:0), and a concomitant accumulation of C(26:0). Moreover, the InhA-inactivated cells, like INH-treated cells, underwent a drastic morphological change, leading to cell lysis. These data show that InhA inactivation, alone, is sufficient to induce the accumulation of saturated fatty acids, cell wall alterations, and cell lysis and are consistent with InhA being a primary target of INH.
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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.