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

Alexander P. Hynes, Geneviève M. Rousseau, Daniel Agudelo, Adeline Goulet, Beatrice Amigues, Jeremy Loehr, Dennis A. Romero, Christophe Fremaux, Philippe Horvath, Yannick Doyon, Christian Cambillau and Sylvain Moineau ()
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Alexander P. Hynes: Université Laval
Geneviève M. Rousseau: Université Laval
Daniel Agudelo: Université Laval
Adeline Goulet: Aix-Marseille Université, Campus de Luminy
Beatrice Amigues: Aix-Marseille Université, Campus de Luminy
Jeremy Loehr: Université Laval
Dennis A. Romero: DuPont Nutrition and Health
Christophe Fremaux: DuPont Nutrition and Health
Philippe Horvath: DuPont Nutrition and Health
Yannick Doyon: Université Laval
Christian Cambillau: Aix-Marseille Université, Campus de Luminy
Sylvain Moineau: Université Laval

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05092-w

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