title: A new group of phage anti-CRISPR genes inhibits the type I-E CRISPR-Cas system of Pseudomonas aeruginosa.
abstract: CRISPR-Cas systems are one of the most widespread phage resistance mechanisms in prokaryotes. Our lab recently identified the first examples of phage-borne anti-CRISPR genes that encode protein inhibitors of the type I-F CRISPR-Cas system of Pseudomonas aeruginosa. A key question arising from this work was whether there are other types of anti-CRISPR genes. In the current work, we address this question by demonstrating that some of the same phages carrying type I-F anti-CRISPR genes also possess genes that mediate inhibition of the type I-E CRISPR-Cas system of P. aeruginosa. We have discovered four distinct families of these type I-E anti-CRISPR genes. These genes do not inhibit the type I-F CRISPR-Cas system of P. aeruginosa or the type I-E system of Escherichia coli. Type I-E and I-F anti-CRISPR genes are located at the same position in the genomes of a large group of related P. aeruginosa phages, yet they are found in a variety of combinations and arrangements. We have also identified functional anti-CRISPR genes within nonprophage Pseudomonas genomic regions that are likely mobile genetic elements. This work emphasizes the potential importance of anti-CRISPR genes in phage evolution and lateral gene transfer and supports the hypothesis that more undiscovered families of anti-CRISPR genes exist. Finally, we provide the first demonstration that the type I-E CRISPR-Cas system of P. aeruginosa is naturally active without genetic manipulation, which contrasts with E. coli and other previously characterized I-E systems. IMPORTANCE The CRISPR-Cas system is an adaptive immune system possessed by the majority of prokaryotic organisms to combat potentially harmful foreign genetic elements. This study reports the discovery of bacteriophage-encoded anti-CRISPR genes that mediate inhibition of a well-studied subtype of CRISPR-Cas system. The four families of anti-CRISPR genes described here, which comprise only the second group of anti-CRISPR genes to be identified, encode small proteins that bear no sequence similarity to previously studied phage or bacterial proteins. Anti-CRISPR genes represent a newly discovered and intriguing facet of the ongoing evolutionary competition between phages and their bacterial hosts.
authors.forename: April
authors.initials: A
authors.lastname: Pawluk
authors.forename: Joseph
authors.initials: J
authors.lastname: Bondy-Denomy
authors.forename: Vivian H W
authors.initials: VH
authors.lastname: Cheung
authors.forename: Karen L
authors.initials: KL
authors.lastname: Maxwell
authors.forename: Alan R
authors.initials: AR
authors.lastname: Davidson
mesh_terms: D064113:CRISPR-Cas Systems; D019143:Evolution, Molecular; D022761:Gene Transfer, Horizontal; D006790:Host-Parasite Interactions; D017105:Pseudomonas Phages / Q000235:genetics* / Q000254:growth & development*; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000821:virology*; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D014764:Viral Proteins
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