title: Inactivation of CRISPR-Cas systems by anti-CRISPR proteins in diverse bacterial species.
abstract: CRISPR-Cas systems provide sequence-specific adaptive immunity against foreign nucleic acids(1,2). They are present in approximately half of all sequenced prokaryotes(3) and are expected to constitute a major barrier to horizontal gene transfer. We previously described nine distinct families of proteins encoded in Pseudomonas phage genomes that inhibit CRISPR-Cas function(4,5). We have developed a bioinformatic approach that enabled us to discover additional anti-CRISPR proteins encoded in phages and other mobile genetic elements of diverse bacterial species. We show that five previously undiscovered families of anti-CRISPRs inhibit the type I-F CRISPR-Cas systems of both Pseudomonas aeruginosa and Pectobacterium atrosepticum, and a dual specificity anti-CRISPR inactivates both type I-F and I-E CRISPR-Cas systems. Mirroring the distribution of the CRISPR-Cas systems they inactivate, these anti-CRISPRs were found in species distributed broadly across the phylum Proteobacteria. Importantly, anti-CRISPRs originating from species with divergent type I-F CRISPR-Cas systems were able to inhibit the two systems we tested, highlighting their broad specificity. These results suggest that all type I-F CRISPR-Cas systems are vulnerable to inhibition by anti-CRISPRs. Given the widespread occurrence and promiscuous activity of the anti-CRISPRs described here, we propose that anti-CRISPRs play an influential role in facilitating the movement of DNA between prokaryotes by breaching the barrier imposed by CRISPR-Cas systems.
authors: Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
authors: April
authors: 0000-0002-6136-2086
authors: A
authors: Pawluk
authors: Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand.
authors: Raymond H J
authors: 0000-0002-5741-9457
authors: RH
authors: Staals
authors: Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand.
authors: Corinda
authors: C
authors: Taylor
authors: Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand.
authors: Bridget N J
authors: BN
authors: Watson
authors: Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
authors: Senjuti
authors: S
authors: Saha
authors: Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand.
authors: Peter C
authors: PC
authors: Fineran
authors: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
authors: Karen L
authors: KL
authors: Maxwell
authors: Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.|Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
authors: Alan R
authors: AR
authors: Davidson
mesh_terms: D001419:Bacteria / Q000201:enzymology*; D001435:Bacteriophages / Q000235:genetics*; D064113:CRISPR-Cas Systems; D004791:Enzyme Inhibitors / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D014764:Viral Proteins