Abstract
Prokaryotic organisms have developed multiple defense systems against phages; however, little is known about whether and how these interact with each other. Here, we studied the connection between two of the most prominent prokaryotic immune systems: restriction-modification and CRISPR. While both systems employ enzymes that cleave a specific DNA sequence of the invader, CRISPR nucleases are programmed with phage-derived spacer sequences, which are integrated into the CRISPR locus upon infection. We found that restriction endonucleases provide a short-term defense, which is rapidly overcome through methylation of the phage genome. In a small fraction of the cells, however, restriction results in the acquisition of spacer sequences from the cleavage site, which mediates a robust type II-A CRISPR-Cas immune response against the methylated phage. This mechanism is reminiscent of eukaryotic immunity in which the innate response offers a first temporary line of defense and also activates a second and more robust adaptive response.
Original language | English (US) |
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Pages (from-to) | 907-919.e7 |
Journal | Molecular cell |
Volume | 82 |
Issue number | 5 |
DOIs | |
State | Published - Mar 3 2022 |
Externally published | Yes |
Keywords
- CRISPR
- Cas9
- bacteriophage
- restriction-modification
- spacer acquisition
- staphylococcus
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology