Evidence map›Paper›PMID 35973427›Full record

ArticleMolecular cell2022

Reactive metabolic byproducts contribute to antibiotic lethality under anaerobic conditions.

Felix Wong, Jonathan M Stokes, Sarah C Bening, Charles Vidoudez, Sunia A Trauger, James J Collins

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
8.3field-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

28 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Article
  3. Synergistic Action of Antimicrobial Peptides and Antibiotics.International journal of molecular sciences · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Bacterial peptidoglycan as a living polymer.Current opinion in chemical biology · 2025
    Review
  16. Characterizing the resistome ofFrontiers in microbiology · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. mBio · 2024
    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

6 authors at 3 institutions in 1 country.

Felix WongInstitute for Medical Engineering & Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jonathan M StokesInstitute for Medical Engineering & Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Sarah C BeningInstitute for Medical Engineering & Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Charles VidoudezHarvard Center for Mass Spectrometry, Harvard University, Cambridge, MA 02138, USA.
Sunia A TraugerHarvard Center for Mass Spectrometry, Harvard University, Cambridge, MA 02138, USA.
James J CollinsInstitute for Medical Engineering & Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. Electronic address: jimjc@mit.edu.
Broad Institute · USHarvard University · USMassachusetts Institute of Technology · US

Funding

Genetic, Metabolic and Regulatory Control of MIC and Relapse in M. tuberculosisR01AI146194 · NIAID · UNIVERSITY OF WASHINGTON · PI ALLAND, DAVID, SHERMAN, DAVID R · 2020 to 2024
$4.1M
NIAID NIH HHS R01 AI146194
6 · The paper itself

Abstract

Understanding how bactericidal antibiotics kill bacteria remains an open question. Previous work has proposed that primary drug-target corruption leads to increased energetic demands, resulting in the generation of reactive metabolic byproducts (RMBs), particularly reactive oxygen species, that contribute to antibiotic-induced cell death. Studies have challenged this hypothesis by pointing to antibiotic lethality under anaerobic conditions. Here, we show that treatment of Escherichia coli with bactericidal antibiotics under anaerobic conditions leads to changes in the intracellular concentrations of central carbon metabolites, as well as the production of RMBs, particularly reactive electrophilic species (RES). We show that antibiotic treatment results in DNA double-strand breaks and membrane damage and demonstrate that antibiotic lethality under anaerobic conditions can be decreased by RMB scavengers, which reduce RES accumulation and mitigate associated macromolecular damage. This work indicates that RMBs, generated in response to antibiotic-induced energetic demands, contribute in part to antibiotic lethality under anaerobic conditions.

Indexed as

Anti-Bacterial AgentsEscherichia coliAnaerobiosisCarbonDNAReactive Oxygen SpeciesAnti-Bacterial AgentsCarbonDNAReactive Oxygen Speciesanaerobicantibiotic resistanceantibioticsantioxidantsmacromolecular damagemass spectrometrymechanism of actionmetabolismreactive electrophilic species

Identifiers

PMID35973427
PMCPMC10149100
OpenAlexW4291582562

What OpenQuestion holds

Textmetadata
LicenceTDM
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.