Bacteriophage genes that inactivate the CRISPR/Cas bacterial immune system

• Published in: Nature (London) Vol. 493; no. 7432; pp. 429 - 432
• Main Authors: Bondy-Denomy, Joe, Pawluk, April, Maxwell, Karen L., Davidson, Alan R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.01.2013; Nature Publishing Group
• Subjects: 631/326/1320; 631/326/1321; 631/326/41/2482; Bacteria; Bacterial genetics; Bacteriology; Bacteriophages; Bacteriophages - genetics; Biological Evolution; Gene Expression Regulation, Viral; Genes; Genes, Bacterial - genetics; Genes, Viral - genetics; Genetic aspects; Genome, Viral - genetics; Humanities and Social Sciences; Immune system; Inverted Repeat Sequences - genetics; letter; Microbiology; Molecular Sequence Data; multidisciplinary; Neutralization; Plasmids; Pseudomonas aeruginosa; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - immunology; Pseudomonas aeruginosa - virology; Science; United States; Canada
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature11723

Five classes of phage genes are identified that protect phages from CRISPR-mediated bacterial immunity. Phage genes deploy 'anti-CRISPR' defence CRISPR/Cas immune systems, widely distributed in bacteria and Archaea, protect microbial cells from phage attack through the use of small RNAs for sequence-specific detection and neutralization of invading genomes. It has been suggested that 'anti-CRISPR' mechanisms might exist, and here Alan Davidson and colleagues identify phage-encoded factors that inhibit the CRISPR/Cas system. They also find homologues of these genes in Pseudomonas species, indicating that anti-CRISPR elements have a critical role in the evolution of this bacterial pathogen. A widespread system used by bacteria for protection against potentially dangerous foreign DNA molecules consists of the clustered regularly interspaced short palindromic repeats (CRISPR) coupled with cas (CRISPR-associated) genes 1 . Similar to RNA interference in eukaryotes 2 , these CRISPR/Cas systems use small RNAs for sequence-specific detection and neutralization of invading genomes 3 . Here we describe the first examples of genes that mediate the inhibition of a CRISPR/Cas system. Five distinct ‘anti-CRISPR’ genes were found in the genomes of bacteriophages infecting Pseudomonas aeruginosa . Mutation of the anti-CRISPR gene of a phage rendered it unable to infect bacteria with a functional CRISPR/Cas system, and the addition of the same gene to the genome of a CRISPR/Cas-targeted phage allowed it to evade the CRISPR/Cas system. Phage-encoded anti-CRISPR genes may represent a widespread mechanism for phages to overcome the highly prevalent CRISPR/Cas systems. The existence of anti-CRISPR genes presents new avenues for the elucidation of CRISPR/Cas functional mechanisms and provides new insight into the co-evolution of phages and bacteria.