Scientists Discover Why a Common Bacteria Stops Wounds From Healing—And How to Fix It

Scientists have uncovered how bacteria repurpose ancient viral machinery to target and attack diverse cell types, including human cells. This groundbreaking discovery explains a long-standing mystery about bacterial injection systems and opens exciting possibilities for precision medicine and targeted drug delivery.

How Do Bacteria Turn Viral Weapons Into Their Own Tools?

At the heart of this discovery are extracellular contractile injection systems (eCISs)—sophisticated molecular machines that bacteria borrowed from viruses called bacteriophages. While viruses originally used these structures to inject their DNA into cells, bacteria have cleverly repurposed them as toxin delivery devices to fight competing organisms like insects and other microbes.

"eCISs look like viral weapons, but they are now fully integrated into bacterial life," the researchers explain. "They are used in ecological battles we are only beginning to understand."

What Makes These Bacterial Weapons So Adaptable?

The research team, led by Professor Asaf Levy from Hebrew University of Jerusalem, developed a new computational algorithm to identify these elusive proteins across thousands of genomes. Their comprehensive analysis revealed 3,445 eCIS tail fiber proteins across 1,069 bacterial and archaeal species—the most complete catalog of its kind.

These bacterial injection systems are built like modular weapons with two key parts:

• Conserved Anchor Domain: A stable "anchor" that attaches the fiber to the bacterial injection particle, remaining consistent across different bacteria
• Variable Receptor-Binding Domain: A rapidly evolving part that determines which specific cell types can be targeted, constantly changing to keep up with targets
• Horizontal Gene Transfer Components: Genetic material acquired from plants, fungi, and even animal immune systems, giving bacteria an expanded toolkit for targeting diverse cells

The team classified these proteins into 1,177 distinct domain families, many predicted to bind sugars and proteins on bacterial or human cell surfaces. Remarkably, genetic evidence suggests bacteria acquired many of these targeting domains through horizontal gene transfer from completely different organisms.

Can These Systems Be Engineered for Medical Use?

To test real-world applications, researchers selected a tail fiber protein from Paenibacillus bacteria that resembles hemagglutinin—a receptor-binding protein found in influenza and measles viruses. They engineered a modified injection system equipped with this fiber and demonstrated it could successfully bind to and inject proteins into human THP-1 monocyte-like cells while leaving other cell types untouched.

The experiments revealed that D-mannose, a sugar naturally found on human cell surfaces, likely acts as a key receptor. When researchers added D-mannose externally, it partially blocked the engineered system from binding to cells. Electron microscopy captured dramatic images of virus-like particles attaching to human cells moments before delivering their molecular payload.

"This is accelerated evolution on steroids," the researchers noted. "Bacteria are essentially sampling the biological world for useful binding tools and repurposing them."

While other research groups and startups are exploring similar engineered systems, this discovery dramatically expands the available toolkit. The thousands of naturally evolved receptor-binding proteins identified could potentially be harnessed to deliver drugs, enzymes, or therapeutic molecules into specific cell types with unprecedented precision.

The study, published in Nature Communications, not only solves fundamental questions about how these bacterial machines function but also demonstrates their potential for biomedical and biotechnological applications. As researchers continue mapping these systems, they're uncovering new possibilities for targeted treatments that could revolutionize how we deliver medicine to exactly where it's needed in the human body.