Research has shed important new light on the ability of bacteria to exchange genes from friend to foe, including genes associated with antimicrobial resistance (AMR).
As researchers at the John Innes Center investigate the strange phenomenon of gene transfer agents (GTAs), they have provided insights that expand our understanding of AMR, a major global health threat.
These gene-carrying particles look like bacteriophages (viruses that infect bacteria), but they were domesticated from ancient viruses and put to beneficial use under the control of bacterial host cells.
They act as couriers, receiving packets of host bacteria’s DNA and delivering it to neighboring bacteria. This “selfless” sharing, known as horizontal gene transfer, can rapidly spread useful traits, such as genes that confer resistance to antibiotics used to treat infectious diseases.
A critical life stage of GTA is host cell lysis. This means that the host cell is destroyed and DNA-filled GTA particles are released. Until now, it was unclear how GTA particles escape from host bacterial cells.
In this study, natural microbiology, The research team used a deep sequencing-based screening method to identify genes important for GTA function in the model bacterium Caulobacter crescentus.
This led to the identification of three gene regulatory hubs, LypABC, that encode bacterial proteins. When these lypABC genes are deleted, the bacteria are unable to lyse and release GTA particles. In contrast, overexpressing the lypABC hub resulted in a much higher proportion of lysed cells. Taken together, these experiments identified LypABC as a regulatory mechanism for GTA-mediated cell lysis.
Remarkably, LypABC resembles the antiphage immune system of bacteria, as it contains protein domains normally required for defense against viruses. However, this collaboration between the John Innes Center, the University of York, and the Rowland Institute at Harvard University suggests that it could be reused to release GTA particles for gene transfer.
They also identified regulatory proteins required to tightly control both GTA activation and GTA-mediated lysis. This control is important because misregulation of LypABC is highly toxic to bacterial cells.
By highlighting the plasticity of bacterial domains, this study advances fundamental knowledge of how gene transfer occurs between bacterial cells and provides important clues for understanding how AMR occurs.
What is particularly interesting is that even though LypABC looks like an immune system, bacteria use it to release GTA particles. This suggests that bacteria can repurpose their immune systems to help share DNA with each other, a process that could contribute to the spread of antibiotic resistance. ”
Dr Emma Banks, John Innes Center Research Fellow, Royal Commission on the 1851 Exhibition
The next step in the research is to discover how the LypABC control hub is activated and how it functions to control bacterial cell destruction and GTA particle release.
“The bacterial CARD-NLR-like immune system controls the release of gene transfer factors.” Natural microbiology.
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Reference magazines:
Banks, E.J. others. (2026). The bacterial CARD-NLR-like immune system controls the release of gene transfer agents. natural microbiology. DOI: 10.1038/s41564-026-02316-4. https://www.nature.com/articles/s41564-026-02316-4.
