Scientists discover retrons in which DNA triggers a bacterial toxin — ScienceDaily

Scientists at Gladstone Institutes have described an unusual mechanism of bacterial defense against viruses: type VI retrons sharply increase the production of single-stranded DNA after bacteriophage infection, which ultimately activates toxin synthesis. The infected bacterium dies, which is expected to stop the virus from reproducing and spreading to neighboring cells, ScienceDaily reports.

DNA does not restrain the toxin but switches it on

Retrons are molecular systems capable of responding to certain viral infections. In previously studied retrons, the toxic protein is already present in the uninfected cell, while short fragments of single-stranded DNA restrain its action. When a phage disrupts this system, the toxin is activated and the bacterium dies.

In type VI retrons, the sequence of events is different. In healthy bacteria, researchers found only trace amounts of single-stranded DNA and detected no noticeable amount of toxin. After the phage enters, DNA production increases substantially. It interacts with RNA that had previously blocked the formation of the toxic protein and removes this restriction.

According to the researchers, the toxin is a very small protein that embeds itself in the bacterial cell membrane and disrupts its stability. In this way, the system triggers the death of the infected cell specifically.

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How the mechanism was discovered

Initially, scientists assumed that type VI retrons might be nonfunctional, as standard methods did not detect the single-stranded DNA characteristic of retrons. At the same time, experiments showed that bacteria with such systems are capable of defending themselves against phages.

To search for the DNA, the team used the Spacer-seq method, developed in the laboratory of the study's senior author, Seth Shipman. The method uses components of the bacterial CRISPR-Cas immune system to record molecular activity in cells. It made it possible to detect a low basal level of DNA production in uninfected cells and its significant increase after infection.

The study was published in the journal Molecular Cell. The authors are also considering whether this natural mechanism can be used to create synthetic molecular sensors, switches for gene activity, or new antimicrobial approaches. Such applications are currently at the research stage.