Bacterias natural self-destruct mechanism used to fight infections

A new study has demonstrated that a natural bacterial defense mechanism against invading viruses can be used as a weapon to combat bacterial infection. The finding opens the door to new anti-bacterial therapeutics, particularly important in the face of rising antibiotic resistance.

When certain bacteria are infected by a virus, they initiate a self-destruct mechanism called the cyclic oligonucleotide-based antiphage signaling system (mercifully shortened to CBASS) to prevent the spread of that virus to other bacterial cells in the population.

Researchers at the Icahn School of Medicine at Mount Sinai have examined this natural bacteria-killing mechanism more closely to see how it works and whether it could be harnessed to control bacterial infections.

The researchers looked particularly at CBASS-associated protein 5 (Cap5) in Pseudomonas bacteria. Cap5 is activated by cyclic nucleotides, small signaling molecules or ‘second messengers’ that are synthesized when a viral infection is sensed and bind to an effector protein to degrade the bacteria’s DNA, causing its death. They were able to obtain high-resolution structures of Cap5 from Pseudomonas in a complex with cyclic nucleotides, uncovering the key to their activation.

Image source: Rechkoblit et al. (2024), Nature Structural & Molecular Biology.