ArticleThe Journal of biological chemistry2012
A novel mechanism of growth phase-dependent tolerance to isoniazid in mycobacteria.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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
30 citing papers in PubMed, 55 citations in OpenAlex.
- Probing Dermal Immunity to Mycobacteria through a Controlled Human Infection Model.ImmunoHorizons · 2024Trial
- Nucleoid-associated protein HU constrains transcription elongation to influence cellular functions, virulence, and drug tolerance in Mycobacterium tuberculosis.Nucleic acids research · 2026Article
- Molecular Kaleidoscope of Nucleoid-Associated Proteins Regulatory Network and Chromosome Architecture in Mycobacterium Tuberculosis.Current microbiology · 2026Review
- PTM-associated condensation of homopolymeric (poly A) RNA by MDP1.Biophysics and physicobiology · 2026Article
- Inactivation of cAMP receptor protein (MSMEG_6189) increases isoniazid susceptibility inJournal of bacteriology · 2025Article
- Genetic stability ofeLife · 2024Article
- Assessing the Impact of Bedaquiline, Clofazimine, and Linezolid on Mycobacterial Genome Integrity.Biomolecules · 2024Article
- Dynamic action of an intrinsically disordered protein in DNA compaction that induces mycobacterial dormancy.Nucleic acids research · 2024Article
- Evaluation of cytokine profiles related toFrontiers in immunology · 2024Article
- Mycobacterial DNA-binding protein 1 is critical for BCG survival in stressful environments and simultaneously regulates gene expression.Scientific reports · 2023Article
- Characterization of spectinamide 1599 efficacy against different mycobacterial phenotypes.Tuberculosis (Edinburgh, Scotland) · 2023Article
- Article
- Transcriptional regulation and drug resistance inFrontiers in cellular and infection microbiology · 2022Review
- HupB, a nucleoid-associated protein, is critical for survival ofFrontiers in microbiology · 2022Article
- Multiform antimicrobial resistance from a metabolic mutation.Science advances · 2021Article
- Mechanisms of Drug-Induced Tolerance in Mycobacterium tuberculosis.Clinical microbiology reviews · 2020Review
- Nucleoid Associated Proteins: The Small Organizers That Help to Cope With Stress.Frontiers in microbiology · 2020Review
- The Isoniazid Paradigm of Killing, Resistance, and Persistence in Mycobacterium tuberculosis.Journal of molecular biology · 2019Review
- Serum antibody profiles in individuals with latent Mycobacterium tuberculosis infection.Microbiology and immunology · 2019Observational
- G-Quadruplex-Forming DNA Aptamers Inhibit the DNA-Binding Function of HupB and Mycobacterium tuberculosis Entry into Host Cells.Molecular therapy. Nucleic acids · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tuberculosis remains one of the most deadly infectious diseases worldwide and is a leading public health problem. Although isoniazid (INH) is a key drug for the treatment of tuberculosis, tolerance to INH necessitates prolonged treatment, which is a concern for effective tuberculosis chemotherapy. INH is a prodrug that is activated by the mycobacterial enzyme, KatG. Here, we show that mycobacterial DNA-binding protein 1 (MDP1), which is a histone-like protein conserved in mycobacteria, negatively regulates katG transcription and leads to phenotypic tolerance to INH in mycobacteria. Mycobacterium smegmatis deficient for MDP1 exhibited increased expression of KatG and showed enhanced INH activation compared with the wild-type strain. Expression of MDP1 was increased in the stationary phase and conferred growth phase-dependent tolerance to INH in M. smegmatis. Regulation of KatG expression is conserved between M. smegmatis and Mycobacterium tuberculosis complex. Artificial reduction of MDP1 in Mycobacterium bovis BCG was shown to lead to increased KatG expression and susceptibility to INH. These data suggest a mechanism by which phenotypic tolerance to INH is acquired in mycobacteria.
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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.