Retrons: Encoding Phage-Defending Toxin/Antitoxin Systems

Retrons: Encoding Phage-Defending Toxin/Antitoxin Systems ...

Retrons are thought to be bacteria genetic retroelements that convert a small RNA to produce multicopy single-stranded DNA (msDNA), but their role has remained unclear. Now, scientists have discovered that some retrons encode toxin proteins, which they keep inactive with the help of a small DNA fragment.

The authors of a new paper demonstrate that a retron of Salmonella TyphimuriumRetron-Sen2 encodes an accessory toxin protein (RcaT) that is neutralized by the RT-msDNA antitoxin complex. This RcaT-containing retron family represents a new kind of toxin/antitoxin systems (TAs).

In the following paper, Bacterial retrons encode phage-defending tripartite toxinantitoxin systems.

Jacob Bobonis, PhD, a former graduate student in the Nassos Typas laboratory, is a co-chair of EMBL's Microbial Ecosystems and Infection Biology transversal themes for more than 30 years.

A previous member of the Typas group discovered that Salmonella cannot grow in colder temperatures without making msDNA. This led to the conclusion that Salmonella cells that are unable to produce msDNA are also sensitive to a lack of oxygen, thus preventing them from colonizing a cows gut.

Bobonis explained that retrons, while more complicated, appeared to be quite similar to other bacteria's toxin/antitoxin systems.

Many bacteria have tens of thousands of toxin/antitoxin systems in their genomes. One gene encodes a toxin that stops the growth of the bacteria, while the other is located right next to the toxin. Bacteria thrive when both coexist, but if the antitoxin is removed, the poison becomes active and inhibits their growth.

Bobonis explains that when we remove the msDNA, the toxin becomes activated. We therefore concluded that the msDNA and the reverse transcriptase represent a new class of antitoxins.

The team developed TAC/TIC (Toxin Activation/Inhibition Conjugation), a high-throughput reverse genetics approach, which allowed them to identify many such proteins of phage origin.

Ultimately, using genetics, proteomics, and bioinformatics, they analyzed the mechanism, and discovered how viral proteins can activate, as well as block, these systems. Retrons can thwart viral invasion at a single-cell level.

Imagine a virus invades just one of the bacteria, then it bursts into the cell, then infects the other nine cells, but the virus does not operate as it does in a cell without the initial infected bacterium. Retrons have protected the rest of the population, according to Bobonis.

The study of antimicrobial resistance provides an approach to understand how these bacteria might be able to inhibit phages. Because these are bacteria's internal suicide mechanisms, we have an angle to develop artificial toxin triggers to externally activate the toxin and kill the cell, said Typas.

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