Evidence map›Paper›PMID 26998690›Full record

ArticleNature genetics2016

A role for the bacterial GATC methylome in antibiotic stress survival.

Nadia R Cohen, Christian A Ross, Saloni Jain, Rebecca S Shapiro, Arnaud Gutierrez, Peter Belenky, Hu Li, James J Collins

Open access · greenAbstract read
In one paragraph

Article in Nature genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
4.9field-weighted citation impact, top 5% 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

68 citing papers in PubMed, 109 citations in OpenAlex.

  1. Review
  2. Replication-coupled hemimethylation inFrontiers in microbiology · 2026
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  11. Decoding the genome and epigenome of avianFrontiers in veterinary science · 2025
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  12. Review
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  16. Microbiology spectrum · 2023
    Article
  17. Article
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  20. Article

8 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

8 authors at 6 institutions in 1 country.

Nadia R CohenWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
Christian A RossDepartment of Molecular Pharmacology and Experimental Therapeutics, Center for Individualized Medicine, Information Technology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Saloni JainInstitute for Medical Engineering and Science, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Rebecca S ShapiroInstitute for Medical Engineering and Science, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Arnaud GutierrezInstitute for Medical Engineering and Science, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Peter BelenkyDepartment of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island, USA.
Hu LiDepartment of Molecular Pharmacology and Experimental Therapeutics, Center for Individualized Medicine, Information Technology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
James J CollinsWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
Massachusetts Institute of Technology · USMayo Clinic · USBroad Institute · USBrown University · USHarvard–MIT Division of Health Sciences and Technology · USHoward Hughes Medical Institute · US

Funding

TRAININGU54GM114838 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI SINHA, SAURABH, SONG, JUN S · 2014 to 2017
$10.8M
A Network Biology Approach to Antibiotic Action and Bacterial Defense MechanismsDP1OD003644 · OD · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI COLLINS, JAMES J · 2007 to 2011
$4.1M
Howard Hughes Medical InstituteNIGMS NIH HHS U54 GM114838NIH HHS DP1 OD003644
6 · The paper itself

Abstract

Antibiotic resistance is an increasingly serious public health threat. Understanding pathways allowing bacteria to survive antibiotic stress may unveil new therapeutic targets. We explore the role of the bacterial epigenome in antibiotic stress survival using classical genetic tools and single-molecule real-time sequencing to characterize genomic methylation kinetics. We find that Escherichia coli survival under antibiotic pressure is severely compromised without adenine methylation at GATC sites. Although the adenine methylome remains stable during drug stress, without GATC methylation, methyl-dependent mismatch repair (MMR) is deleterious and, fueled by the drug-induced error-prone polymerase Pol IV, overwhelms cells with toxic DNA breaks. In multiple E. coli strains, including pathogenic and drug-resistant clinical isolates, DNA adenine methyltransferase deficiency potentiates antibiotics from the β-lactam and quinolone classes. This work indicates that the GATC methylome provides structural support for bacterial survival during antibiotic stress and suggests targeting bacterial DNA methylation as a viable approach to enhancing antibiotic activity.

Indexed as

DNA MethylationAdenineDNA, BacterialDrug Resistance, BacterialEscherichia coliStress, PhysiologicalAdenineDNA, Bacterial

Identifiers

PMID26998690
PMCPMC4848143
OpenAlexW2309553472

What OpenQuestion holds

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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.