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Virus helps bacteria evade immune system

3D computer-generated image of Pseudomonas aeruginosa bacteria, which can cause chronic wound infections. CDC/James Archer

Infected wounds that can’t heal properly can cause pain, hospitalization, and even death. Often, the bacteria that cause these infections are resistant to antibiotics. Preventing such infections is a major public health priority.

One bacterium that causes chronic wound infections, called Pseudomonas aeruginosa (Pa), is often infected by a bacteriophage (or phage)—a type of virus that targets bacteria. Some phages kill the bacteria they infect. Others—like the one that infects Pa, called Pf phage—use the bacteria to copy themselves but don’t kill them in the process.

Researchers led by Dr. Paul Bollyky from the Stanford University School of Medicine had previously found that Pa can harness Pf phages to help produce biofilms. Biofilms are complex, multi-layered microbial communities that provide a protective haven for germs in the body. The infectious phages thus help the bacteria survive.

To further understand the role that these phages play in Pa wound infections, the research team first tested wounds in patients at their hospital for phage-infected Pa. Their work was funded in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). Results were published on March 29, 2019, in Science.

Out of 37 patients in their hospital with chronic Pa infections, 25 (68%) also had phage in their wounds. The longer a wound had gone without healing, the more likely it was to harbor phage-infected Pa.

In mice, phage-infected Pa were more likely to infect wounds and to prove fatal than Pa that didn’t harbor phage.

Filamentous Pf bacteriophages under an electron microscope. University of Montana

The researchers used cultured immune cells to look closely at immune cell interactions with Pa. They found that the the phages served as decoys for the immune system. Immune cells used virus-fighting mechanisms to engage the phages instead of mounting an attack on the bacteria. The result was that Pa infections could flourish.

The team tested two therapies in mice to see if they could keep phage-infected Pa from establishing itself in wounds. One was a vaccine using part of a protein on the surface of the Pf phage. Another was a ready-made antibody against the phage.

Both therapies reduced the risk of Pa wound infection by about half. Surprisingly, the strategies seemed to work by causing the immune system to activate its bacteria-fighting mechanisms. The researchers suggest that this reaction might be directed at phage stuck to the surface of the bacteria.

In addition to identifying potential strategies to reduce wound infections, these findings suggest that phages may also interact with human immune cells to affect other types of bacterial infections.

“We’ve long known that you’ve got up to 10 quadrillion phages in your body, but we just figured whatever they were doing was strictly between them and the bacteria in your body,” Bollyky says. “Now we know that phages can get inside your cells, too, and make you sick.”

—by Sharon Reynolds