Type III CRISPR-Cas provides resistance against nucleus-forming jumbo phages via abortive infection

Bacteria have diverse defenses against phages. In response, jumbo phages evade multiple DNA-targeting defenses by protecting their DNA inside a nucleus-like structure. We previously demonstrated that RNA-targeting type III CRISPR-Cas systems provide jumbo phage immunity by recognizing viral mRNA exported from the nucleus for translation. Here, we demonstrate that recognition of phage mRNA by the type III system activates a cyclic triadenylate-dependent accessory nuclease, NucC. Although unable to access phage DNA in the nucleus, NucC degrades the bacterial chromosome, triggers cell death, and disrupts phage replication and maturation. Hence, type-III-mediated jumbo phage immunity occurs via abortive infection, with suppression of the viral epidemic protecting the population. We further show that type III systems targeting jumbo phages have diverse accessory nucleases, including RNases that provide immunity. Our study demonstrates how type III CRISPR-Cas systems overcome the inaccessibility of jumbo phage DNA to provide robust immunity.

Automated summary

Bacteria have diverse defenses against phages, but jumbo phages can avoid these defenses by protecting their DNA inside a nucleus-like structure. This study reveals that RNA-targeting type III CRISPR-Cas systems provide immunity to jumbo phages by recognizing viral mRNA in the cell for translation. The recognition of phage mRNA activates an accessory nuclease that degrades the bacterial chromosome, triggers cell death, and disrupts phage replication and maturation. This type of immunity is achieved via abortive infection, suppressing the viral epidemic and protecting the bacterial population.