Scientists have revealed new details about how bacteria share genes, including genes that cause antimicrobial resistance (AMR), a growing global health threat. The discovery comes from researchers at the John Innes Center who studied unusual particles known as gene transfer agents (GTAs).
GTAs are similar to bacteriophages (viruses that infect bacteria), but they are no longer harmful invaders. Instead, they are derived from ancient viruses that bacteria adapted and brought under their control.
Virus-like particles carry DNA between cells
These particles act like tiny delivery vehicles. They take pieces of DNA from one bacterial cell and transport them to other nearby bacterial cells. This process, called horizontal gene transfer, allows bacteria to quickly share useful traits, such as genes that help them withstand antibiotic treatment.
A key step in this process is host cell lysis, which breaks up the bacterial cells and allows them to release GTA particles. Until now, scientists didn’t fully understand how these particles escaped from their host cells.
Major gene clusters controlling cell lysis
In a study published in natural microbiologyThe research team used a screening method based on deep sequencing to identify genes involved in GTA activity in model bacteria. Caulobacter crescentus.
They identified a three-gene system called LypABC that produces bacterial proteins. When the lypABC gene is removed, the cells can no longer break down and release GTA particles. When the system was overactivated, many cells lysed. These results indicate that LypABC acts as a central control hub for this process.
Immune system repurposed for gene transfer
One of the most surprising discoveries is that LypABC closely resembles the antiphage immune system of bacteria. It usually contains protein components associated with defense against viruses. However, in this case, the system appears to have been repurposed to aid in the release of GTA particles and facilitate gene transfer.
The research, conducted in collaboration with the University of York and the Rowland Institute at Harvard University, reveals how bacteria can reuse existing biological systems in unexpected ways.
Strict regulations are essential to survival
The researchers also discovered regulatory proteins that help tightly control GTA activity. This control is critical because inappropriate activation of LypABC can be highly toxic to bacterial cells.
This study provides deeper insight into how genes move between cells by revealing how flexible bacterial systems are. This process plays a major role in the spread of antibiotic resistance.
New clues in the fight against antibiotic resistance
Dr Emma Banks, lead author of the study and Royal 1851 Exhibition Commission Research Fellow, said: “What is particularly interesting is that LypABC looks like the immune system, but bacteria use it to release GTA particles. This suggests that bacteria can repurpose the immune system to help share DNA with each other. This process may contribute to the spread of antibiotic resistance.”
The next step is to understand how the LypABC system is activated and how it controls bacterial cell rupture to release GTA particles.
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.
Dr Emma Banks, lead author of the study and Royal 1851 Exhibition Commission Research Fellow, said: “What is particularly interesting is that LypABC looks like the immune system, but bacteria use it to release GTA particles. This suggests that bacteria can repurpose the immune system to help share DNA with each other. This process may contribute to the spread of antibiotic resistance.”
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.
