USA, Oct 20: The researchers have uncovered a new way bacteria detect viral attacks: a virus-produced enzyme cuts a bacterial sensor protein, triggering a self-destructing immune response.
The discovery could lead to more effective phage therapies against antibiotic-resistant bacteria and provide insight into ancient immune mechanisms shared with humans, as per the ScienceDaily.
Scientists searching for new ways to treat bacterial infections are increasingly turning to viruses known as bacteriophages (phages). These viruses specifically target bacteria, allowing them to kill harmful microbes without damaging human cells. They can also attack bacteria that have developed resistance to antibiotics.
Phage therapy, however, faces a major obstacle. Bacteria are not defenceless against viruses. They have evolved their own immune systems, and understanding those defences could help scientists develop therapeutic phages that are better able to overcome them.
According to the ScienceDaily, a new research has now identified an important way bacteria recognise a viral attack. Scientists found that a viral enzyme cuts a crucial sensor molecule inside the bacterial cell. That damage serves as an alarm, activating an immune response.
The discovery could ultimately help researchers develop more effective phage therapies capable of avoiding bacterial immune defenses.
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"This is one of the most common forms of bacterial immunity, so when we finally figured it out, it was a total eureka moment," says Sam Hobbs, PhD, assistant professor of biochemistry at University of Utah Health and the first author on a paper describing the research.
The results are published in Science.
The study focused on a bacterial immune system called CBASS. When activated, CBASS can trigger an extreme "last resort" response in which an infected bacterium kills itself before the invading virus has a chance to spread to nearby cells, as per the ScienceDaily website.
Because activating this defence is fatal to the bacterium, the system must be able to recognise a genuine viral threat with great precision.
Hobbs and his colleagues found that this detection process relies on something the virus itself needs. Certain phages produce an enzyme that becomes the signal that alerts the bacterium to the attack.
"Certain kinds of phages have a protein called a protease, which degrades other proteins. 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 signalling pathway," added Hobbs.
This form of virus detection is notably different from related antiviral immune systems. Some of those pathways recognise viral genetic material directly. In CBASS, the trigger instead comes from the activity of a viral protein acting on a protein belonging to the bacterial host.
"This is a totally new mechanism for how these host proteins are activated. I never would have guessed that this was the way it was going to work," said Hobbs.
The finding not only sheds light on how bacteria defend themselves from phages, but could also have implications for understanding immunity in humans.
CBASS is related to an immune pathway found in people, suggesting that aspects of this antiviral defence have survived across an enormous span of evolutionary history. The connection indicates that the pathway dates back at least to the common ancestor shared by bacteria and humans.
Bacteria also give researchers a useful experimental system for investigating fundamental questions about immunity. Their rapid life cycles allow scientists to study immune processes quickly, then test what they learn in biological models that are 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. It's incredibly fascinating, and it's a cool window into what's important in maintaining the ability to fight viruses," added Hobbs as quoted by ScienceDaily website.
This research is published in Science as "Phage proteases activate CBASS antiphage immunity."