A new study published in Nature Communications details how bacteria have adapted virus-derived injection systems to recognize and attach to diverse cell types. This research, led by Prof. Asaf Levy of the Hebrew University of Jerusalem and doctoral researcher Nimrod Nachmias, with collaborators from Beijing, identifies thousands of rapidly evolving receptor-binding proteins. The findings explain how these bacterial systems can be continuously retargeted in nature by swapping the cell-binding component.
The findings explain how these bacterial systems can be continuously retargeted in nature by swapping the cell-binding component.
Key Discovery
Extracellular contractile injection systems (eCISs), which are sophisticated virus-like molecular machines originating from bacteriophage tails, are central to the discovery. While viruses utilize these structures for cell infection, bacteria have repurposed them to deliver toxins against competing host organisms, such as insects and microbes.
Solving a Mystery
Identifying the specialized receptor-binding proteins, known as tail fiber proteins, for eCISs has been challenging due to their rapid evolution. The research team developed a new computational algorithm to locate these genes across numerous genomes. They identified 3,445 eCIS tail fiber proteins within 2,585 eCIS gene operons across 1,069 bacterial and archaeal species.
The study revealed that eCIS tail fibers consist of two distinct parts:
- A conserved "anchor" domain that attaches the fiber to the eCIS particle.
- A highly variable receptor-binding domain that determines target cell types.
Genetic evidence suggests many of these variable domains were acquired through horizontal gene transfer from diverse sources, including other bacteria, viruses, plants, fungi, and components of animal immune systems.
This phenomenon of frequent gene acquisition from eukaryotes into a specific gene is considered rare.
Demonstrating Potential
To validate the findings, researchers engineered a chimeric eCIS particle. They equipped it with a candidate tail fiber from a Paenibacillus eCIS, which resembles hemagglutinin (a receptor-binding protein found in influenza and measles viruses).
This engineered eCIS demonstrated the ability to bind to and inject proteins into human THP-1 monocyte-like cells, while avoiding other cell types. Experiments indicated that D-mannose, a sugar on human cell surfaces, might serve as a key receptor.
Future Implications
This discovery significantly expands the available toolkit for future biomedical and biotechnological applications. The thousands of naturally evolved receptor-binding proteins uncovered could be utilized to deliver drugs, enzymes, or other therapeutic molecules into specific cell types.
The study also opens avenues for further fundamental biological research into the natural functions and deployment conditions of these systems.