Evidence map›Paper›PMID 36695586›Full record

ArticlemBio2023

Peptidyl tRNA Hydrolase Is Required for Robust Prolyl-tRNA Turnover in Mycobacterium tuberculosis.

Francesca G Tomasi, Jessica T P Schweber, Satoshi Kimura, Junhao Zhu, Laura A T Cleghorn, Susan H Davis, Simon R Green, Matthew K Waldor, Eric J Rubin

Open access · goldAbstract read
In one paragraph

Article in mBio, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

7 citing papers in PubMed, 9 citations in OpenAlex.

  1. Association ofPathogens (Basel, Switzerland) · 2026
    Article
  2. ACS omega · 2025
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. RNA biology · 2023
    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

9 authors at 3 institutions in 2 countries.

Francesca G Tomasi *Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.ORCID 0000-0003-1421-9284
Jessica T P Schweber *Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
Satoshi Kimura *Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Junhao ZhuDepartment of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
Laura A T CleghornDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
Susan H DavisDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
Simon R GreenDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
Matthew K WaldorDepartment of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
Eric J RubinDepartment of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.ORCID 0000-0001-5120-962X
Harvard University · USUniversity of Dundee · GBBrigham and Women's Hospital · US

Funding

Vulnerabilities in Mycobacterial Cell-Wall BiogenesisP01AI095208 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI SACCHETTINI, JAMES C · 2012 to 2022
$19.8M
Vibrio cholerae intestinal colonization and vaccine developmentR01AI042347 · NIAID · TUFTS UNIVERSITY BOSTON · PI WALDOR, MATTHEW K · 1998 to 2025
$7.3M
Mechanisms of macrolide synergy in Mycobacterium tuberculosisF31AI167560 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI TOMASI, FRANCESCA GUGLIELMINI · 2022 to 2022
$22k
HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) 1F31AI167560-01HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) P01AI095208NIAID NIH HHS F31 AI167560NIAID NIH HHS P01 AI095208NIAID NIH HHS R01 AI042347
6 · The paper itself

Abstract

Enzymes involved in rescuing stalled ribosomes and recycling translation machinery are ubiquitous in bacteria and required for growth. Peptidyl tRNA drop-off is a type of abortive translation that results in the release of a truncated peptide that is still bound to tRNA (peptidyl tRNA) into the cytoplasm. Peptidyl tRNA hydrolase (Pth) recycles the released tRNA by cleaving off the unfinished peptide and is essential in most bacteria. We developed a sequencing-based strategy called copper sulfate-based tRNA sequencing (Cu-tRNAseq) to study the physiological role of Pth in Mycobacterium tuberculosis (Mtb). While most peptidyl tRNA species accumulated in a strain with impaired Pth expression, peptidyl prolyl-tRNA was particularly enriched, suggesting that Pth is required for robust peptidyl prolyl-tRNA turnover. Reducing Pth levels increased Mtb's susceptibility to tRNA synthetase inhibitors that are in development to treat tuberculosis (TB) and rendered this pathogen highly susceptible to macrolides, drugs that are ordinarily ineffective against Mtb. Collectively, our findings reveal the potency of Cu-tRNAseq for profiling peptidyl tRNAs and suggest that targeting Pth would open new therapeutic approaches for TB.

Indexed as

Amino Acyl-tRNA SynthetasesMycobacterium tuberculosisCarboxylic Ester HydrolasesHydrolasesPeptidesRNA, TransferAmino Acyl-tRNA SynthetasesCarboxylic Ester HydrolasesHydrolasesPeptidesRNA, Transferantibiotic resistancebacterial geneticsMycobacterium tuberculosisribosomestranslationtRNAtRNA sequencing

Identifiers

PMID36695586
PMCPMC9973355
OpenAlexW4317939694

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.