PMID:28041849

Citation	Rauch, BJ, Silvis, MR, Hultquist, JF, Waters, CS, McGregor, MJ, Krogan, NJ and Bondy-Denomy, J (2017) Inhibition of CRISPR-Cas9 with Bacteriophage Proteins. Cell 168:150-158.e10
Abstract	Bacterial CRISPR-Cas systems utilize sequence-specific RNA-guided nucleases to defend against bacteriophage infection. As a countermeasure, numerous phages are known that produce proteins to block the function of class 1 CRISPR-Cas systems. However, currently no proteins are known to inhibit the widely used class 2 CRISPR-Cas9 system. To find these inhibitors, we searched cas9-containing bacterial genomes for the co-existence of a CRISPR spacer and its target, a potential indicator for CRISPR inhibition. This analysis led to the discovery of four unique type II-A CRISPR-Cas9 inhibitor proteins encoded by Listeria monocytogenes prophages. More than half of L. monocytogenes strains with cas9 contain at least one prophage-encoded inhibitor, suggesting widespread CRISPR-Cas9 inactivation. Two of these inhibitors also blocked the widely used Streptococcus pyogenes Cas9 when assayed in Escherichia coli and human cells. These natural Cas9-specific "anti-CRISPRs" present tools that can be used to regulate the genome engineering activities of CRISPR-Cas9.
Links	PubMed PMC5235966 Online version:10.1016/j.cell.2016.12.009
Keywords	Bacterial Proteins/antagonists & inhibitors; Bacteriophages/metabolism; CRISPR-Associated Protein 9; CRISPR-Cas Systems; Endonucleases/antagonists & inhibitors; Escherichia coli; Genetic Engineering; HEK293 Cells; Humans; Listeria monocytogenes/enzymology; Listeria monocytogenes/immunology; Listeria monocytogenes/virology; Prophages
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
LISMN:A0A247D711		GO:0110133: negative regulation of CRISPR-cas system	ECO:0007150:		P		Figure 3 (C) acrIIA4 often occurred in the absence of acrIIA1 homologs in phages and mobile elements of Listeria monocytogenes	complete

References

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