Conditional tolerance of temperate phages via transcription-dependent CRISPR-Cas targeting.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE

Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.

Transcription, Genetic*; Bacteriophages/*genetics ; Bacteriophages/*physiology ; CRISPR-Cas Systems/*genetics ; CRISPR-Cas Systems/*physiology ; Staphylococcus epidermidis/*genetics ; Staphylococcus epidermidis/*virology; Bacteriophages/immunology ; Bacteriophages/pathogenicity ; Base Sequence ; CRISPR-Associated Proteins/immunology ; CRISPR-Associated Proteins/metabolism ; CRISPR-Cas Systems/immunology ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats/immunology ; DNA, Viral/genetics ; DNA, Viral/immunology ; DNA, Viral/metabolism ; Immune Tolerance ; Lysogeny/genetics ; Lysogeny/immunology ; Molecular Sequence Data ; Proviruses/genetics ; Proviruses/immunology ; Proviruses/pathogenicity ; Proviruses/physiology ; Staphylococcus epidermidis/immunology

A fundamental feature of immune systems is the ability to distinguish pathogenic from self and commensal elements, and to attack the former but tolerate the latter. Prokaryotic CRISPR-Cas immune systems defend against phage infection by using Cas nucleases and small RNA guides that specify one or more target sites for cleavage of the viral genome. Temperate phages include viruses that can integrate into the bacterial chromosome, and they can carry genes that provide a fitness advantage to the lysogenic host. However, CRISPR-Cas targeting that relies strictly on DNA sequence recognition provides indiscriminate immunity both to lytic and lysogenic infection by temperate phages-compromising the genetic stability of these potentially beneficial elements altogether. Here we show that the Staphylococcus epidermidis CRISPR-Cas system can prevent lytic infection but tolerate lysogenization by temperate phages. Conditional tolerance is achieved through transcription-dependent DNA targeting, and ensures that targeting is resumed upon induction of the prophage lytic cycle. Our results provide evidence for the functional divergence of CRISPR-Cas systems and highlight the importance of targeting mechanism diversity. In addition, they extend the concept of 'tolerance to non-self' to the prokaryotic branch of adaptive immunity.

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DP2 AI104556 United States AI NIAID NIH HHS; T32 AI070084 United States AI NIAID NIH HHS

0 (CRISPR-Associated Proteins)
0 (DNA, Viral)

Date Created: 20140902 Date Completed: 20141204 Latest Revision: 20211021

20221213

PMC4214910

10.1038/nature13637

25174707