Scientists have discovered a new family of bacterial defence systems that use enzymes called nucleotidyltransferases (NTase) to produce DNA signals and defend against phage infection. The system, named Hailong, consists of two proteins: HalB and HalA.
HalB is an NTase enzyme that converts deoxy-ATP into single-stranded DNA oligomers. This process triggers a response in the cell, which activates the HalA protein complex. However, instead of activating the immune response, the HalA complex becomes repressed by binding to the DNA signal produced by HalB.
The discovery was made using X-ray crystal structures and cryo-electron microscopy (cryo-EM) techniques. The researchers found that the HalA complex forms a unique crown-shaped domain that binds the DNA signal and gates its activation.
In a surprising twist, the scientists found that viral DNA exonucleases required for phage replication trigger the release of the primed HalA complex, leading to protective host cell growth arrest. This suggests that the Hailong system acts as a molecular “guard” against phage infection, producing inhibitory nucleotide immune signals.
The discovery expands our understanding of how NTase enzymes are used by bacteria to control antiviral immunity and provides new insights into the mechanisms of bacterial defences against phage infections.
Source: https://www.nature.com/articles/s41586-025-09058-z