Evidence map›Paper›PMID 19028890›Full record

ArticleJournal of bacteriology2009

Function and regulation of class I ribonucleotide reductase-encoding genes in mycobacteria.

Mohube B Mowa, Digby F Warner, Gilla Kaplan, Bavesh D Kana, Valerie Mizrahi

Open access · greenAbstract read
In one paragraph

Article in Journal of bacteriology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

26 citing papers in PubMed, 59 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Metabolic Rewiring ofMetabolites · 2024
    Review
  5. Article
  6. Article
  7. Quantitative proteomic reveals gallium maltolate induces an iron-limited stress response and reduced quorum-sensing in Pseudomonas aeruginosa.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020
    Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. The class Ib ribonucleotide reductase from Mycobacterium tuberculosis has two active R2F subunits.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2014
    Article
  17. Article
  18. Ribonucleotide reductases: essential enzymes for bacterial life.Frontiers in cellular and infection microbiology · 2014
    Review
  19. Article
  20. Article
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

5 authors at 4 institutions in 2 countries.

Mohube B MowaMRC/NHLS/WITS Molecular Mycobacteriology Research Unit, DST/NRF Centre of Excellence for Biomedical TB Research, School of Pathology, University of the Witwatersrand, National Health Laboratory Service, Johannesburg 2000, South Africa.
Digby F Warner
Gilla Kaplan
Bavesh D Kana
Valerie Mizrahi
International Center for Public Health · USInternational Center for Public Health · USNational Health Laboratory Service · ZAUniversity of the Witwatersrand · ZA

Funding

TUBERCULOSIS SUPPLEMENTD43TW000231 · FIC · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI ABDOOL KARIM, QUARRAISHA · 1993 to 2014
$13.1M
Host &Pathogen Determinants of M tuberculosis LatencyR01AI054338 · NIAID · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI KAPLAN, GILLA · 2002 to 2011
$5.0M
Regulation of Early Cytokine Receptors to TB InfectionR01AI054361 · NIAID · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI KAPLAN, GILLA · 2002 to 2006
$1.9M
FIC NIH HHS 5 D43 TW00231FIC NIH HHS D43 TW000231Howard Hughes Medical InstituteNIAID NIH HHS AI54361NIAID NIH HHS R01 AI054338NIAID NIH HHS R01 AI054361NIAID NIH HHS R01 AI54338
6 · The paper itself

Abstract

Ribonucleotide reductases (RNRs) are crucial to all living cells, since they provide deoxyribonucleotides (dNTPs) for DNA synthesis and repair. In Mycobacterium tuberculosis, a class Ib RNR comprising nrdE- and nrdF2-encoded subunits is essential for growth in vitro. Interestingly, the genome of this obligate human pathogen also contains the nrdF1 (Rv1981c) and nrdB (Rv0233) genes, encoding an alternate class Ib RNR small (R2) subunit and a putative class Ic RNR R2 subunit, respectively. However, the role(s) of these subunits in dNTP provision during M. tuberculosis pathogenesis is unknown. In this study, we demonstrate that nrdF1 and nrdB are dispensable for the growth and survival of M. tuberculosis after exposure to various stresses in vitro and, further, that neither gene is required for growth and survival in mice. These observations argue against a specialist role for the alternate R2 subunits under the conditions tested. Through the construction of nrdR-deficient mutants of M. tuberculosis and Mycobacterium smegmatis, we establish that the genes encoding the essential class Ib RNR subunits are specifically regulated by an NrdR-type repressor. Moreover, a strain of M. smegmatis mc(2)155 lacking the 56-kb chromosomal region, which includes duplicates of nrdHIE and nrdF2, and a mutant retaining only one copy of nrdF2 are shown to be hypersensitive to the class I RNR inhibitor hydroxyurea as a result of depleted levels of the target. Together, our observations identify a potential vulnerability in dNTP provision in mycobacteria and thereby offer a compelling rationale for pursuing the class Ib RNR as a target for drug discovery.

Indexed as

AnimalsAnti-Bacterial AgentsBacterial ProteinsBase SequenceFemaleGene Expression Regulation, BacterialGenetic Complementation TestGenome, BacterialHydroxyureaMiceMicrobial Sensitivity TestsModels, GeneticMolecular Sequence DataMutagenesisMycobacteriumMycobacterium smegmatisAnti-Bacterial AgentsBacterial ProteinsHydroxyureaNrdF protein, bacteriaRibonucleotide Reductases

Identifiers

PMID19028890
PMCPMC2632068
OpenAlexW2156886311

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.