ArticleThe Journal of infectious diseases2015
Transcriptional Adaptation of Drug-tolerant Mycobacterium tuberculosis During Treatment of Human Tuberculosis.
Article in The Journal of infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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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
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Effects of Respiratory Isolation for Tuberculosis to Reduce Community-based Transmission: A Systematic Review.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Pooled it
- A Dose-Finding Study to Guide Use of Verapamil as an Adjunctive Therapy in Tuberculosis.Clinical pharmacology and therapeutics · 2024Trial
- Impact of the Mycobaterium africanum West Africa 2 Lineage on TB Diagnostics in West Africa: Decreased Sensitivity of Rapid Identification Tests in The Gambia.PLoS neglected tropical diseases · 2016Trial
- Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials.BMC medicine · 2016Trial
- The Cyclic Di-GMP Receptor HpoR Modulates Mycobacterial Multidrug Susceptibility by Regulating IniBAC-Mediated Envelope Permeability.Microorganisms · 2026Article
- Defining the Mechanism of Action and Resistance of NewACS chemical biology · 2026Article
- Profiling of BDQ-induced transcriptome suggests amino acid metabolism and stress responses as alternate mechanisms contributing to BDQ tolerance inMicrobiology spectrum · 2026Article
- Predictors of culture status in patients with persistent smear-positive pulmonary tuberculosis at two months of treatment.BMC infectious diseases · 2026Article
- Transcript-Capture sequencing enriches mRNA ofNAR molecular medicine · 2026Article
- Transcript-Capture sequencing enriches mRNA ofbioRxiv : the preprint server for biology · 2025Article
- Community-Based Tuberculosis Isolation Decisions Require Individualization Based on Effectiveness and Duration of Treatment, Community Risks, and Patient Harms.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
- Emergence of antibiotic-specificAntimicrobial agents and chemotherapy · 2025Article
- Assessing Infectiousness and the Impact of Effective Treatment to Guide Isolation Recommendations for People With Pulmonary Tuberculosis.The Journal of infectious diseases · 2025Review
- Respiratory Isolation for Tuberculosis: A Historical Perspective.The Journal of infectious diseases · 2025Article
- Genetic stability ofeLife · 2024Article
- Emergence of antibiotic-specificbioRxiv : the preprint server for biology · 2024Article
- Bacterial persisters: molecular mechanisms and therapeutic development.Signal transduction and targeted therapy · 2024Review
- Transcriptomic responses to antibiotic exposure inAntimicrobial agents and chemotherapy · 2024Article
- NTCA Guidelines for Respiratory Isolation and Restrictions to Reduce Transmission of Pulmonary Tuberculosis in Community Settings.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Article
- Revolutionizing control strategies against Mycobacterium tuberculosis infection through selected targeting of lipid metabolism.Cellular and molecular life sciences : CMLS · 2023Review
4 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
22 authors at 8 institutions in 3 countries.
Funding
Abstract
backgroundTreatment initiation rapidly kills most drug-susceptible Mycobacterium tuberculosis, but a bacterial subpopulation tolerates prolonged drug exposure. We evaluated drug-tolerant bacilli in human sputum by comparing messenger RNA (mRNA) expression of drug-tolerant bacilli that survive the early bactericidal phase with treatment-naive bacilli.
methodsM. tuberculosis gene expression was quantified via reverse-transcription polymerase chain reaction in serial sputa from 17 Ugandans treated for drug-susceptible pulmonary tuberculosis.
resultsWithin 4 days, bacterial mRNA abundance declined >98%, indicating rapid killing. Thereafter, the rate of decline slowed >94%, indicating drug tolerance. After 14 days, 16S ribosomal RNA transcripts/genome declined 96%, indicating slow growth. Drug-tolerant bacilli displayed marked downregulation of genes associated with growth, metabolism, and lipid synthesis and upregulation in stress responses and key regulatory categories-including stress-associated sigma factors, transcription factors, and toxin-antitoxin genes. Drug efflux pumps were upregulated. The isoniazid stress signature was induced by initial drug exposure, then disappeared after 4 days.
conclusionsTranscriptional patterns suggest that drug-tolerant bacilli in sputum are in a slow-growing, metabolically and synthetically downregulated state. Absence of the isoniazid stress signature in drug-tolerant bacilli indicates that physiological state influences drug responsiveness in vivo. These results identify novel drug targets that should aid in development of novel shorter tuberculosis treatment regimens.
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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.