Karen Zhang, a PhD student in Seth Shipman’s lab and the study’s lead author, said the newly identified mechanism is “almost the mirror-image version of how we traditionally view retrons, because the DNA switches on toxin production instead of inhibiting an already-produced toxin.”
Researchers at Gladstone Institutes have identified what they call type VI retrons, a bacterial immune system that reverses the established logic of these defences. The findings were published in Molecular Cell.
Bacteria have evolved specialised protections against phages, viruses that target bacterial cells. In known retron systems, a toxin is continually present in an uninfected cell and held back by small single-stranded DNA molecules.
When a retron detects an attack by a particular phage strain, it releases a toxic protein that kills the infected cell. That self-destruction protects the wider bacterial colony.
Type VI retrons take the opposite route. In uninfected cells, they produce no noticeable levels of either toxin or single-stranded DNA.
They begin making single-stranded DNA only after a phage enters the cell. That DNA then turns on toxin production, rather than repressing toxin that already exists.
Shipman, a Gladstone Investigator and senior author of the study, called type VI retrons “by far, the strangest of the retron systems that we or anyone else has come across”.
He said the systems use “Rube Goldberg-level complexity, using molecular mechanisms that we would never have thought to invent, but that we'll use in future technologies.”
Retrons can efficiently modify and deliver single-stranded DNA, a property that researchers are seeking to use in more efficient DNA-editing tools for human health and therapies.
Shipman’s team is working to use retrons to rewrite disease-causing mutations inside human cells with unprecedented precision.
The researchers used Spacer-seq, a tool previously developed in Shipman’s lab. It uses molecular components of CRISPR-Cas to create a record of gene activity inside a cell.
Shipman’s lab is also developing synthetic sensors and switches based on type VI retrons to control gene activity. Scientists are exploring ways to incorporate type VI retron toxins into new antimicrobial therapies.
Comments (0)