Evidence map›Paper›PMID 41139285›Full record

ArticleACS synthetic biology2025

Design of Specific Peptide Inhibitors of Toxin-Antitoxin-Mediated Antiphage Defense.

Dia A Ghose, Sebastian R Swanson, Foster Birnbaum, Dustin Britton, Jessie L Gan, Emily M Mahoney, Michael T Laub, Amy E Keating

Abstract read
In one paragraph

Article in ACS synthetic biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

8 authors.

Dia A GhoseDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.ORCID 0009-0001-4040-630X
Sebastian R SwansonDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Foster BirnbaumDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Dustin BrittonDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Jessie L GanDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Emily M MahoneyDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Michael T LaubDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Amy E KeatingDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

Funding

Computational and Experimental Investigation and Design of Protein Interaction SpecificityR35GM149227 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI AMY E KEATING · 2023 to 2026
$2.2M
Howard Hughes Medical InstituteNIGMS NIH HHS R35 GM149227
6 · The paper itself

Abstract

Toxin-antitoxin (TA) systems are widespread antiphage defense elements in bacteria that may impede successful phage therapy. Phage-encoded inhibitors of these systems have been discovered that enhance phage infection capacity. We used fragment-based design with deep-learning scoring functions to design peptide inhibitors of the toxin RelE. Our peptides extend a fragment of the native RelB antitoxin and are sufficient to inhibit RelE toxicity. Successful inhibitors share a highly conserved binding mode that mimics the native antitoxin but have diverse sequences, with alternative contacts used to form the peptide-protein interface. Designed peptides show different interaction specificities toward RelE family proteins, distinct from the wild-type RelB antitoxin, and inhibit the antiphage defense activity of multiple orthologous RelBE systems. This work showcases the use of structure-based computational design to generate peptide binders that serve as potential counter-defense elements.

Indexed as

AntitoxinsBacterial ToxinsBacteriophagesPeptidesToxin-Antitoxin SystemsDrug DesignEscherichia coliEscherichia coli ProteinsAntitoxinsBacterial ToxinsEscherichia coli ProteinsPeptidesantiphage defenseinteraction specificitypeptidephage therapyprotein designtoxin−antitoxin

Identifiers

PMID41139285
PMCPMC12739935

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Registered trials

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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.