University of Utah Health researchers have discovered that bacteria detect viruses when a viral enzyme cuts an important sensor molecule, kicking off the immune response. Published in Science, the findings pave the way for development of better phage therapies that can evade the bacterial immune system.
Bacteriophages, or phages, are a group of viruses that can attack and kill dangerous bacteria while leaving human cells unharmed and bypassing antibiotic resistance. Yet, bacteria possess defenses against viruses. Learning how these immune defenses work can help researchers develop better disease-fighting viruses.
Inside the CBASS Final Safeguard
Triggering a “last resort” immune defense to destroy the bacterium before viruses can spread to adjacent cells is the function of a bacterial immune system component known as CBASS. With such a dire consequence for the bacterium, precise sensing of the viral trigger is a necessity.
The sensing mechanism spots a molecule required for viral survival, according to Sam Hobbs, PhD, assistant professor of biochemistry at University of Utah Health and the first author on a paper describing the research.
A Brand-New Paradigm for Cellular Defense
“Certain kinds of phages have a protein called a protease, which degrades other proteins,” Hobbs explains. “We found that the protease from the phage actually acts directly on the host protein, and that is the signal that turns on the whole signaling pathway.”
Unlike related antiviral immune pathways that respond to the presence of viral genetic material, this system relies on a distinctly different activation trigger. “This is a totally new mechanism for how these host proteins are activated,” Hobbs says. “I never would have guessed that this was the way it was going to work.”
Deep Evolutionary Links to Human Immunity
Understanding CBASS may also advance our knowledge of the human immune system. Because CBASS shares similarities with a comparable human immune pathway, this mechanism appears to have endured since the time bacteria and humans shared a common ancestor. Researchers can leverage the swift life cycle of bacteria to rapidly investigate immune function questions, subsequently testing those insights in models more closely related to humans.
“The fact that these systems are conserved between bacteria and humans suggests that they’ve been maintained in these different organisms for that entire evolutionary trajectory,” Hobbs says. “The cells are telling us that this is a really important pathway because they’ve maintained it for billions of years.”
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