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Nat Commun. 2018 Jul 25;9(1):2919. doi: 10.1038/s41467-018-05092-w.

Widespread anti-CRISPR proteins in virulent bacteriophages inhibit a range of Cas9 proteins.

Author information

1
Département de biochimie, de microbiologie, et de bioinformatique, Faculté des sciences et de génie, Groupe de recherche en écologie buccale, Faculté de médecine dentaire, Université Laval, Québec City, QC, G1V 0A6, Canada.
2
Farncombe Family Digestive Health Research Institute, McMaster University. Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, L8S 4K1, Canada.
3
Centre Hospitalier Universitaire de Québec Research Center, Université Laval, Québec City, QC, G1V 4G2, Canada.
4
Architecture et Fonction des Macromolécules Biologiques, Aix-Marseille Université, Campus de Luminy, Case 932, 13288, Marseille Cedex 09, France.
5
Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique (CNRS), Campus de Luminy, Case 932, 13288, Marseille Cedex 09, France.
6
DuPont Nutrition and Health, 3329 Agriculture Dr, Madison, WI, 53716, USA.
7
DuPont Nutrition and Health, BP 10, 86220, Dangé-Saint-Romain, France.
8
Département de biochimie, de microbiologie, et de bioinformatique, Faculté des sciences et de génie, Groupe de recherche en écologie buccale, Faculté de médecine dentaire, Université Laval, Québec City, QC, G1V 0A6, Canada. sylvain.moineau@bcm.ulaval.ca.
9
Félix d'Hérelle Reference Center for Bacterial Viruses, Faculté de médecine dentaire, Université Laval, Québec City, QC, G1V 0A6, Canada. sylvain.moineau@bcm.ulaval.ca.

Abstract

CRISPR-Cas systems are bacterial anti-viral systems, and bacterial viruses (bacteriophages, phages) can carry anti-CRISPR (Acr) proteins to evade that immunity. Acrs can also fine-tune the activity of CRISPR-based genome-editing tools. While Acrs are prevalent in phages capable of lying dormant in a CRISPR-carrying host, their orthologs have been observed only infrequently in virulent phages. Here we identify AcrIIA6, an Acr encoded in 33% of virulent Streptococcus thermophilus phage genomes. The X-ray structure of AcrIIA6 displays some features unique to this Acr family. We compare the activity of AcrIIA6 to those of other Acrs, including AcrIIA5 (also from S. thermophilus phages), and characterize their effectiveness against a range of CRISPR-Cas systems. Finally, we demonstrate that both Acr families from S. thermophilus phages inhibit Cas9-mediated genome editing of human cells.

PMID:
30046034
PMCID:
PMC6060171
DOI:
10.1038/s41467-018-05092-w
[Indexed for MEDLINE]
Free PMC Article

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