Bacteria detect a phage when its own enzyme cuts their sensor protein

The defence works by watching for the phage's protease, an enzyme the virus cannot easily abandon. Certain phages carry a protease, an enzyme that breaks down other proteins, and the virus needs it to replicate ^[5]. Instead of scanning for the virus's genes, the bacterium reacts to what that enzyme does ^[5].

Sam Hobbs, an assistant professor of biochemistry at University of Utah Health and the paper's first author, described the signal ^[14]. "Certain kinds of phages have a protein called a protease, which degrades other proteins," he said. "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." ^[6]

That is a different trigger from the one several related defences use, which read viral genetic material directly ^[7]. Here the alarm is the viral enzyme's action on a protein that belongs to the bacterium ^[7].

"This is a totally new mechanism for how these host proteins are activated," Hobbs said. "I never would have guessed that this was the way it was going to work." ^[8]

Because that response is fatal to the cell, the bacterium cannot afford a false alarm, and tying detection to an enzyme the phage has to produce is a way to be sure the attack is real ^[4][5].

The pathway reaches well beyond bacteria. CBASS resembles an immune pathway in humans, which the researchers say indicates it dates back at least to the common ancestor the two share ^[10]. "The cells are telling us that this is a really important pathway because they've maintained it for billions of years," Hobbs said ^[11].

The release does not say whether a phage can be engineered to evade CBASS, name the sensor protein, or show how a redesigned phage would fare against a bacterium running CBASS. It describes how bacteria detect the attack. The payoff the authors point to, phages that avoid tripping the alarm, is a direction for future work ^[13][15].