Evidence map›Paper›PMID 24100503›Full record

ArticleAntimicrobial agents and chemotherapy2013

Functional role of methylation of G518 of the 16S rRNA 530 loop by GidB in Mycobacterium tuberculosis.

Sharon Y Wong, Babak Javid, Balasubrahmanyam Addepalli, Grzegorz Piszczek, Michael Brad Strader, Patrick A Limbach, Clifton E Barry

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
1.3field-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

35 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
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  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Multidrug-resistant tuberculosis.Nature reviews. Disease primers · 2024
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Computational and structural biotechnology journal · 2023
    Article
  16. Interactions between host epithelial cells andEmerging microbes & infections · 2022
    Article
  17. Article
  18. Article
  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

7 authors at 3 institutions in 2 countries.

Sharon Y WongTuberculosis Research Section, Laboratory of Clinical Infectious Disease, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA.
Babak Javid
Balasubrahmanyam Addepalli
Grzegorz Piszczek
Michael Brad Strader
Patrick A Limbach
Clifton E Barry
National Institutes of Health · USUniversity of Cincinnati · USTsinghua University · CN

Funding

Biophysics FacilityZICHL000338 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI PISZCZEK, GRZEGORZ · 2009 to 2025
$12.2M
Exploring the metabolism of non-replicating and drug-resistant TBZIAAI000783 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BARRY, CLIFTON · 2009 to 2017
$8.2M
International Research in Korea: Clinical Studies of Drug-Resistant TuberculosisZIAAI001067 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BARRY, CLIFTON · 2009 to 2017
$6.9M
UPLC for Enhanced Mass Spectrometry of Modified RNAsR01GM058843 · NIGMS · UNIVERSITY OF CINCINNATI · PI LIMBACH, PATRICK A · 1999 to 2025
$5.1M
Mass Spectrometry of Ribosomal RNA:Protein InteractionsR56GM058843 · NIGMS · UNIVERSITY OF CINCINNATI · PI LIMBACH, PATRICK A · 2009 to 2009
$330k
Intramural NIH HHSMedical Research Council G0601934NIGMS NIH HHS GM58843NIGMS NIH HHS R01 GM058843NIGMS NIH HHS R56 GM058843
6 · The paper itself

Abstract

Posttranscriptional modifications of bacterial rRNA serve a variety of purposes, from stabilizing ribosome structure to preserving its functional integrity. Here, we investigated the functional role of one rRNA modification in particular-the methylation of guanosine at position 518 (G518) of the 16S rRNA in Mycobacterium tuberculosis. Based on previously reported evidence that G518 is located 5 Å; from proline 44 of ribosomal protein S12, which interacts directly with the mRNA wobble position of the codon:anticodon helix at the A site during translation, we speculated that methylation of G518 affects protein translation. We transformed reporter constructs designed to probe the effect of functional lesions at one of the three codon positions on translational fidelity into the wild-type strain, H37Rv, and into a ΔgidB mutant, which lacks the methyltransferase (GidB) that methylates G518. We show that mistranslation occurs less in the ΔgidB mutant only in the construct bearing a lesion in the wobble position compared to H37Rv. Thus, the methylation of G518 allows mistranslation to occur at some level in order for translation to proceed smoothly and efficiently. We also explored the role of methylation at G518 in altering the susceptibility of M. tuberculosis to streptomycin (SM). Using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), we confirmed that G518 is not methylated in the ΔgidB mutant. Furthermore, isothermal titration calorimetry experiments performed on 70S ribosomes purified from wild-type and ΔgidB mutant strains showed that methylation significantly enhances SM binding. These results provide a mechanistic explanation for the low-level, SM-resistant phenotype observed in M. tuberculosis strains that contain a gidB mutation.

Indexed as

Bacterial ProteinsDNA MethylationMass SpectrometryMethyltransferasesMycobacterium tuberculosisProtein Structure, SecondaryRNA, Ribosomal, 16SBacterial ProteinsMethyltransferasesRNA, Ribosomal, 16S

Identifiers

PMID24100503
PMCPMC3837903
OpenAlexW2163667700

What OpenQuestion holds

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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.