ArticleJournal of bacteriology2000
The stringent response of Mycobacterium tuberculosis is required for long-term survival.
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 168 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.
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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
168 citing papers in PubMed, 1 synthesis or guideline pooled it, 340 citations in OpenAlex.
- Identification of gene targets against dormant phase Mycobacterium tuberculosis infections.BMC infectious diseases · 2007Pooled it
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- Growth-rate dependent response of mycobacteria to relief of inhibition by a bacteriostatic antibiotic.FEMS microbiology letters · 2026Article
- Unraveling the start element and regulatory divergence of core promoters across the domain bacteria.Nucleic acids research · 2025Article
- MIP3α-RelVaccine · 2025Article
- Bacterial persisters: molecular mechanisms and therapeutic development.Signal transduction and targeted therapy · 2024Review
- Mycobacterial biofilms: A therapeutic target against bacterial persistence and generation of antibiotic resistance.Heliyon · 2024Review
- Gene Regulatory Mechanism of Mycobacterium Tuberculosis during Dormancy.Current issues in molecular biology · 2024Review
- Article
- Rel-dependent decrease in the expression of ribosomal protein genes by inhibition of the respiratory electron transport chain inFrontiers in microbiology · 2024Article
- Tale of Twin Bifunctional Second Messenger (p)ppGpp Synthetases and Their Function in Mycobacteria.ACS omega · 2023Review
- Growth-rate dependency of ribosome abundance and translation elongation rate in Corynebacterium glutamicum differs from that in Escherichia coli.Nature communications · 2023Article
- Starvation sensing by mycobacterial RelA/SpoT homologue through constitutive surveillance of translation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Mycobacterial Regulatory Systems Involved in the Regulation of Gene Expression Under Respiration-Inhibitory Conditions.Journal of microbiology (Seoul, Korea) · 2023Review
- Review
- Termination factor Rho mediates transcriptional reprogramming of Bacillus subtilis stationary phase.PLoS genetics · 2023Article
- Review
- Noise in a Metabolic Pathway Leads to Persister Formation in Mycobacterium tuberculosis.Microbiology spectrum · 2022Article
- Structural variations between small alarmone hydrolase dimers support different modes of regulation of the stringent response.The Journal of biological chemistry · 2022Article
- InJournal of bacteriology · 2022Article
108 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
6 authors at 4 institutions in 2 countries.
Funding
Abstract
The stringent response utilizes hyperphosphorylated guanine [(p)ppGpp] as a signaling molecule to control bacterial gene expression involved in long-term survival under starvation conditions. In gram-negative bacteria, (p)ppGpp is produced by the activity of the related RelA and SpoT proteins. Mycobacterium tuberculosis contains a single homolog of these proteins (Rel(Mtb)) and responds to nutrient starvation by producing (p)ppGpp. A rel(Mtb) knockout strain was constructed in a virulent strain of M. tuberculosis, H37Rv, by allelic replacement. The rel(Mtb) mutant displayed a significantly slower aerobic growth rate than the wild type in synthetic liquid media, whether rich or minimal. The growth rate of the wild type was equivalent to that of the mutant when citrate or phospholipid was employed as the sole carbon source. These two organisms also showed identical growth rates within a human macrophage-like cell line. These results suggest that the in vivo carbon source does not represent a stressful condition for the bacilli, since it appears to be utilized in a similar Rel(Mtb)-independent manner. In vitro growth in liquid media represents a condition that benefits from Rel(Mtb)-mediated adaptation. Long-term survival of the rel(Mtb) mutant during in vitro starvation or nutrient run out in normal media was significantly impaired compared to that in the wild type. In addition, the mutant was significantly less able to survive extended anaerobic incubation than the wild-type virulent organism. Thus, the Rel(Mtb) protein is required for long-term survival of pathogenic mycobacteria under starvation conditions.
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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.