CRISPR-Cas10 can flood virally infected bacteria with toxic molecules, researchers discover

CRISPR-Cas9 has long been likened to a kind of genetic scissors, thanks to its ability to snip out any desired section of DNA with elegant precision. But it turns out that CRISPR systems have more than one strategy in their toolkit.

A mechanism originally discovered in bacteria, where it has operated as an adaptive immune system for eons, CRISPR is naturally deployed by certain singled-cell organisms to protect themselves against viruses (called phages) and other foreign genetic fragments.

Now, researchers at Rockefeller's Laboratory of Bacteriology – headed by Luciano Marraffini, and at the MSKCC's Structural Biology Laboratory headed by Dinshaw Patel – have discovered how one CRISPR system battles invaders with not only genetic scissors, but also acts as a sort of molecular fumigator.

In a recent publication in Cell, the scientists found that this system, called CRISPR-Cas10, floods a virally infected bacterium with toxic molecules, and thus prevents the virus from spreading through the rest of the bacterial population.

In CRISPR systems, guide RNAs identify problematic genetic material, and the enzymes begin snipping. However, the CRISPR-Cas10 complex also produces a burst of small second messenger molecules called cyclic-oligoadenylates (cOAs), which help shut down cell activity, thereby preventing the virus from spreading. This second line of attack is akin to fumigating one pest-ridden room, and then quickly shutting the door to keep the infestation contained so it can't spread to the rest of the house.

Image source: Baca et al. (2024), Cell.