ArticlePloS one2015
Mycobacterium tuberculosis Is Resistant to Isoniazid at a Slow Growth Rate by Single Nucleotide Polymorphisms in katG Codon Ser315.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Growth arrest of Mycobacterium tuberculosis in acidic environments enhances their survival of antibiotic treatment.PLoS biology · 2026Article
- Role of Small Non-Coding RNA in Gram-Negative Bacteria: New Insights and Comprehensive Review of Mechanisms, Functions, and Potential Applications.Molecular biotechnology · 2025Review
- Increased proportion of growth-arrested bacilli in acidic pH adaptation promotesbioRxiv : the preprint server for biology · 2025Article
- A comparative study of antibiotic resistance patterns in Mycobacterium tuberculosis.Scientific reports · 2025Article
- Decoding drug tolerance: insights into theFrontiers in microbiology · 2025Article
- EfpA is required for regrowth ofAntimicrobial agents and chemotherapy · 2024Article
- Transcriptome analysis and molecular characterization of novel small RNAs in Mycobacterium tuberculosis Lineage 1.World journal of microbiology & biotechnology · 2024Article
- Metabolic Rewiring ofMetabolites · 2024Review
- Clustering minimal inhibitory concentration data through Bayesian mixture models: An application to detectStatistical methods in medical research · 2023Article
- NSC19723, a Thiacetazone-Like Benzaldehyde Thiosemicarbazone Improves the Efficacy of TB DrugsMicrobiology spectrum · 2022Article
- Small Noncoding RNAs and Their Role in the Pathogenesis of Mycobacterium tuberculosis Infection.Biochemistry. Biokhimiia · 2021Review
- Mechanisms of Drug-Induced Tolerance in Mycobacterium tuberculosis.Clinical microbiology reviews · 2020Review
- Re-growth ofAntimicrobial agents and chemotherapy · 2019Article
- AlteredFrontiers in microbiology · 2018Article
- Isoniazid Killing of Mycobacterium smegmatis NADH Pyrophosphatase Mutant at Single-Cell Level using Microfluidics and Time-Lapse Microscopy.Scientific reports · 2017Article
- Mutations in catalase-peroxidase KatG from isoniazid resistant Mycobacterium tuberculosis clinical isolates: insights from molecular dynamics simulations.Journal of molecular modeling · 2017Article
- Isoniazid-resistant tuberculosis: a cause for concern?The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2017Review
- Roles of Regulatory RNAs for Antibiotic Resistance in Bacteria and Their Potential Value as Novel Drug Targets.Frontiers in microbiology · 2017Review
- Potential and use of bacterial small RNAs to combat drug resistance: a systematic review.Infection and drug resistance · 2017Review
- Diverse drug-resistant subpopulations of Mycobacterium tuberculosis are sustained in continuous culture.Journal of the Royal Society, Interface · 2016Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An important aim for improving TB treatment is to shorten the period of antibiotic therapy without increasing relapse rates or encouraging the development of antibiotic-resistant strains. In any M. tuberculosis population there is a proportion of bacteria that are drug-tolerant; this might be because of pre-existing populations of slow growing/non replicating bacteria that are protected from antibiotic action due to the expression of a phenotype that limits drug activity. We addressed this question by observing populations of either slow growing (constant 69.3h mean generation time) or fast growing bacilli (constant 23.1h mean generation time) in their response to the effects of isoniazid exposure, using controlled and defined growth in chemostats. Phenotypic differences were detected between the populations at the two growth rates including expression of efflux mechanisms and the involvement of antisense RNA/small RNA in the regulation of a drug-tolerant phenotype, which has not been explored previously for M. tuberculosis. Genotypic analyses showed that slow growing bacilli develop resistance to isoniazid through mutations specifically in katG codon Ser315 which are present in approximately 50-90% of all isoniazid-resistant clinical isolates. The fast growing bacilli persisted as a mixed population with katG mutations distributed throughout the gene. Mutations in katG codon Ser315 appear to have a fitness cost in vitro and particularly in fast growing cultures. Our results suggest a requirement for functional katG-encoded catalase-peroxide in the slow growers but not the fast-growing bacteria, which may explain why katG codon Ser315 mutations are favoured in the slow growing cultures.
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