Evidence map›Paper›PMID 10940033›Full record

ArticleJournal of bacteriology2000

The stringent response of Mycobacterium tuberculosis is required for long-term survival.

T P Primm, S J Andersen, V Mizrahi, D Avarbock, H Rubin, C E Barry

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
168citing papers in PubMed, 1 pooled it
7.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

168 citing papers in PubMed, 1 synthesis or guideline pooled it, 340 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. MIP3α-RelVaccine · 2025
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  6. Bacterial persisters: molecular mechanisms and therapeutic development.Signal transduction and targeted therapy · 2024
    Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. 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 · 2023
    Article
  14. Review
  15. Review
  16. Article
  17. Microorganisms · 2022
    Review
  18. Article
  19. Article
  20. InJournal of bacteriology · 2022
    Article

108 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 2 countries.

T P PrimmTuberculosis Research Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20852, USA.
S J Andersen
V Mizrahi
D Avarbock
H Rubin
C E Barry
South African Institute for Medical Research · ZAUniversity of Pennsylvania · USNational Institute of Allergy and Infectious Diseases · USNational Institutes of Health · US

Funding

Pathogenesis, Latency and Drug Resistance Of Mycobacterium TuberculosisZ01AI000783 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI BARRY, CLIFTON · 1997 to 2008
$5.8M
REGULATION OF DORMANCY IN M TUBERCULOSISR01AI043420 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI RUBIN, HARVEY · 1999 to 2003
$1.3M
Intramural NIH HHS Z01 AI000783NIAID NIH HHS R01 AI043420NIAID NIH HHS R01-AI43420
6 · The paper itself

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.

Indexed as

Cell LineCulture MediaGenotypeGuanosine PentaphosphateHumansLigasesMacrophagesMutagenesisMycobacterium tuberculosisPhenotypeTime FactorsCulture Mediaguanosine 3',5'-polyphosphate synthetasesGuanosine PentaphosphateLigases

Identifiers

PMID10940033
PMCPMC111369
OpenAlexW2116738290

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.