Degenerate target sites mediate rapid primed CRISPR adaptation

• DOI: 10.1073/pnas.1400071111
• Publication Date: 2014-04-08T04:10:32Z
• Authors: Peter C. Fineran; Matthias J. H. Ge...; María Suárez-Diez; Tim Künne; Jos Boekhorst; Sacha A. F. T. va...; Raymond H. J. Staals; Stan J. J. Brouns
• Keywords: Base Pair Mismatch; Molecular Sequence Data; interference; bacterial immunity; 03 medical and health sciences; Databases, Genetic; Clustered Regularly Interspaced Short Palindromic Repeats; Nucleotide Motifs; streptococcus-thermophilus; cas systems; Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; 0303 health sciences; Base Sequence; Escherichia coli K12; adaptive immune-systems; foreign dna; High-Throughput Screening Assays; 3. Good health; dual-rna; RNA, Bacterial; Mutation; defense system; escherichia-coli; recognition; Plasmids

Significance Bacteria are constantly exposed to foreign elements, such as bacteriophages and plasmids. The CRISPR-Cas (clustered regularly interspaced short palindromic repeats–CRISPR associated) adaptive immune systems provide heritable sequence-specific protection against these invaders. To develop immunity, bacteria add segments of foreign nucleic acid to their CRISPR memory. However, phage and plasmid mutants can evade CRISPR-Cas recognition by altering their targeted sequence. CRISPR-Cas responds to evasion by quickly generating immunity by acquiring new pieces of invader genome. We determined that this rapid generation of resistance is promiscuous, with recognition of highly diverged or related elements eliciting new immunity. Our results demonstrate that CRISPR-Cas systems are more robust than previously thought and, not only have a highly specific resistance memory, but also have a broad ability to identify divergent genetic elements.