'Insane in the membrane': 2',3'-cGAMP triggers filamentous phage defense

Megan Wang1, Samuel H Sternberg2

  • 1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.

Cell Host & Microbe
|April 9, 2026
PubMed

Insights

Bacteria produce a signaling molecule, 2

Area of Science:

  • Microbiology
  • Molecular Biology
  • Immunology

Background:

  • The signaling molecule 2',3'-cyclic guanosine monophosphate (cGAMP) was previously thought to be exclusive to animals.
  • Bacterial defense mechanisms against phages are crucial for microbial survival.

Purpose of the Study:

  • To investigate the production and function of 2',3'-cGAMP in bacteria.
  • To explore the evolutionary origins of cGAS-STING-like signaling pathways.

Main Methods:

  • Bacterial strain analysis
  • Molecular cloning
  • Biochemical assays
  • Microscopy

Main Results:

  • Bacteria were found to produce 2',3'-cGAMP.
  • This molecule activates a SAVED-domain effector protein.
  • The activated effector forms filaments that disrupt bacterial membranes, leading to abortive infection and preventing phage replication.

Conclusions:

  • The discovery of 2',3'-cGAMP production in bacteria expands its known evolutionary distribution.
  • This finding reveals a novel bacterial defense system against bacteriophages.
  • It suggests a broader evolutionary history for cGAS-STING-like signaling pathways than previously understood.

Related Concept Videos

DNA Bacteriophages01:26

DNA Bacteriophages

Bacteriophages, or phages, are viruses that specifically infect bacteria, utilizing their genetic material to hijack host cellular machinery for replication. DNA bacteriophages employ single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) genomes. These phages exhibit diverse replication strategies and host interactions, influencing their ecological roles and applications in biotechnology and medicine.ssDNA BacteriophagesssDNA phages, with their small genomes, utilize unique strategies to...
1.5K
Viral Replication: Lytic Cycle01:20

Viral Replication: Lytic Cycle

Bacteriophages, or phages, are viruses that specifically infect bacteria. Among them, T-even bacteriophages, such as T4, exhibit a well-characterized lytic replication cycle in Escherichia coli (E. coli). This process ensures the rapid proliferation of the virus while ultimately leading to the destruction of the bacterial host.Attachment and DNA InjectionThe infection process begins with the recognition and binding of the T4 phage to the E. coli cell surface. Tail fibers of the phage...
2.7K
CRISPR and crRNAs02:53

CRISPR and crRNAs

Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
20.3K
Regulation of Bacterial Virulence01:28

Regulation of Bacterial Virulence

Pathogenic bacteria employ a range of regulatory mechanisms to modulate the expression of virulence genes in response to environmental and host-derived signals. These mechanisms ensure that virulence factors are expressed only under favorable conditions, thereby optimizing infection and survival strategies.Mechanisms of Virulence RegulationKey regulatory strategies include:Two-Component Systems: These consist of a membrane-bound sensor kinase and a cytoplasmic response regulator. Environmental...
47
Lysogenic Cycle of Bacteriophages00:43

Lysogenic Cycle of Bacteriophages

In contrast to the lytic cycle, phages infecting bacteria via the lysogenic cycle do not immediately kill their host cell. Instead, they combine their genome with the host genome, allowing the bacteria to replicate the phage DNA along with the bacterial genome. The incorporated copy of the phage genome is called the prophage. Some prophages can re-activate and enter the lytic cycle. This often occurs in response to a perturbation, such as DNA damage, but can also transpire in the absence of...
69.7K
Viral Replication: Lysogenic Cycle01:16

Viral Replication: Lysogenic Cycle

The lysogenic cycle is a crucial viral replication strategy that allows bacteriophages to persist within host cells without immediately destroying them. This process is primarily observed in temperate phages, such as bacteriophage lambda (λ), which infects Escherichia coli. The cycle allows the viral genome to persist across bacterial generations while keeping host cells viable.Integration of the Viral GenomeUpon infection, bacteriophage lambda attaches to the bacterial surface and injects...
2.5K