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A bacteriophage encodes its own CRISPR/Cas adaptive response to evade host innate immunity



Bacteriophages (or phages) are the most abundant biological entities on earth, and are estimated to outnumber their bacterial prey by tenfold1. The constant threat of phage predation has led to the evolution of a broad range of bacterial immunity mechanisms that in turn result in the evolution of diverse phage immune evasion strategies, leading to a dynamic co-evolutionary arms race2,3. Although bacterial innate immune mechanisms against phage abound, the only documented bacterial adaptive immune system is the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system, which provides sequence-specific protection from invading nucleic acids, including phage4,5,6,7,8,9,10,11. Here we show a remarkable turn of events, in which a phage-encoded CRISPR/Cas system is used to counteract a phage inhibitory chromosomal island of the bacterial host. A successful lytic infection by the phage is dependent on sequence identity between CRISPR spacers and the target chromosomal island. In the absence of such targeting, the phage-encoded CRISPR/Cas system can acquire new spacers to evolve rapidly and ensure effective targeting of the chromosomal island to restore phage replication.

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Figure 1: Genomic organization of the ICP1 CRISPR/Cas system.
Figure 2: Genomic organization of PLE1, a representative V. cholerae PLE targeted by the CRISPR/Cas system of ICP1-related phages.
Figure 3: Sequence-based targeting by the ICP1 CRISPR/Cas system is essential for lytic growth on V. cholerae PLE+.

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Data deposits

The sequences for the CRISPR/Cas system in ICP1_2011_A and ICP1_2006_E have been deposited at GenBank (accession numbers KC152959 and KC152958, respectively). The sequences for the V. cholerae PLEs identified in clinical isolates from the ICDDR,B have been deposited at GenBank/EMBL/DDBJ under the accession numbers KC152960 (PLE1) and KC152961 (PLE2).


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The authors thank the Tufts University Core Facility for sequencing and computational support. This work was supported by US National Institutes of Health grants AI055058 (A.C.), AI045746 (A.C.) and AI058935 (S.B.C.). A.C. is a Howard Hughes Medical Institute Investigator.

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Authors and Affiliations



K.D.S. and D.W.L. performed experiments. K.D.S., D.W.L. and A.C. designed experiments. K.D.S. and A.C. wrote the manuscript. S.B.C. provided materials. All authors discussed the results and commented on the manuscript.

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Correspondence to Andrew Camilli.

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The authors declare no competing financial interests.

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Seed, K., Lazinski, D., Calderwood, S. et al. A bacteriophage encodes its own CRISPR/Cas adaptive response to evade host innate immunity. Nature 494, 489–491 (2013).

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