Evidence map›Paper›PMID 41903528›Full record

ArticleCell host & microbe2026

Bacterial 2',3'-cGAMP activates a SAVED effector to form membrane-disrupting filaments and restrict phage replication.

Uday Tak, Kate Schinkel, Peace Walth, Jian Wei Tay, Erik W Hartwick, Aaron T Whiteley

Abstract read
In one paragraph

Article in Cell host & microbe, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Crystal structure of the cytosolic Nudix-like domain of CD-NTase-associated protein 16 from Enterococcus faecalis.Acta crystallographica. Section F, Structural biology communications · 2026
    Article
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Uday TakDepartment of Biochemistry, University of Colorado Boulder, Boulder, CO, USA.
Kate SchinkelDepartment of Biochemistry, University of Colorado Boulder, Boulder, CO, USA.
Peace WalthDepartment of Biochemistry, University of Colorado Boulder, Boulder, CO, USA.
Jian Wei TayBioFrontiers Institute, University of Colorado Boulder, Boulder, CO, USA.
Erik W HartwickDepartment of Biochemistry, University of Colorado Boulder, Boulder, CO, USA.
Aaron T WhiteleyDepartment of Biochemistry, University of Colorado Boulder, Boulder, CO, USA. Electronic address: aaron.whiteley@colorado.edu.

Funding

COORDINATE REGULATION OF BACTERIAL VIRULENCE FACTORSR01AI026289 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MEKALANOS, JOHN JOSEPH · 1988 to 2018
$8.3M
Genetic Analysis of Toxinogenesis in Vibrio CholeraeR01AI018045 · NIAID · HARVARD MEDICAL SCHOOL · PI MEKALANOS, JOHN JOSEPH · 2009 to 2018
$6.7M
Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)DP2AT012346 · NCCIH · UNIVERSITY OF COLORADO · PI WHITELEY, AARON THOMAS · 2022 to 2025
$2.4M
Modernization/operational improvements to basic centrifugation infrastructure of the Shared Instruments Pool in the Department of Biochemistry University of Colorado BoulderR24OD033699 · OD · UNIVERSITY OF COLORADO · PI ERBSE, ANNETTE H · 2022 to 2022
$143k
Microscale Thermophoresis - Monolith NT.115S10OD021603 · OD · UNIVERSITY OF COLORADO · PI TAATJES, DYLAN J · 2016 to 2016
$138k
NCCIH NIH HHS DP2 AT012346NIAID NIH HHS R01 AI018045NIAID NIH HHS R01 AI026289NIH HHS R24 OD033699NIH HHS S10 OD021603
6 · The paper itself

Abstract

Mammalian cells initiate antiviral signaling when cyclic GMP-AMP synthase (cGAS) detects cytoplasmic DNA and synthesizes 2',3'-cyclic GMP-AMP (2',3'-cGAMP), which activates stimulator of interferon genes (STING). Similarly, bacteria use cyclic oligonucleotide-based antiphage signaling systems (CBASS) to detect phage using ancestral cGAS/DncV-like nucleotidyltransferases (CD-NTases), but they are not known to use 2',3'-cGAMP. Here, we discover a bacterial CD-NTase that produces 2',3'-cGAMP to activate a Saf-2TM-SMODS-associated fused to various effector domains (SAVED) effector (CD-NTase-associated protein 14 [Cap14]), which initiates membrane disruption to restrict phage replication. Cryo-electron microscopy (cryo-EM) reveals that Cap14 binds 2',3'-cGAMP to form a filament, while electrophysiology suggests that cGAMP activates membrane disruption. Swapping the Cap14 transmembrane domain with a nuclease domain yields a functional chimera that exclusively responds to 2',3'-cGAMP. We hypothesize that other predicted transmembrane effectors in CBASS operons disrupt membranes, and we confirm this by showing that bacterial STING homologs with transmembrane domains restrict phage through membrane disruption. These findings expand our understanding of cGAS-STING-like pathways in bacterial immunity.

Indexed as

BacteriaBacteriophagesNucleotides, CyclicVirus ReplicationBacterial ProteinsCell MembranecGAS-STING Signaling PathwayCryoelectron MicroscopyHumansInnate Immunity RecognitionMembrane ProteinsNucleotidyltransferasesSignal TransductionBacterial Proteinscyclic guanosine monophosphate-adenosine monophosphateMembrane ProteinsNucleotides, CyclicNucleotidyltransferases2TM-STINGantiphageCap13Cap14CBASScGAMPcGASinnate immunityphageSaf-2TM-SAVED

Identifiers

PMID41903528
PMCPMC13085583

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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.