Abstract:
:Bacterial CRISPR-Cas systems employ RNA-guided nucleases to destroy phage (viral) DNA. Phages, in turn, have evolved diverse "anti-CRISPR" proteins (Acrs) to counteract acquired immunity. In Listeria monocytogenes, prophages encode two to three distinct anti-Cas9 proteins, with acrIIA1 always present. However, the significance of AcrIIA1's pervasiveness and its mechanism are unknown. Here, we report that AcrIIA1 binds with high affinity to Cas9 via the catalytic HNH domain. During lysogeny in Listeria, AcrIIA1 triggers Cas9 degradation. During lytic infection, however, AcrIIA1 fails to block Cas9 due to its multi-step inactivation mechanism. Thus, phages encode an additional Acr that rapidly binds and inactivates Cas9. AcrIIA1 also uniquely inhibits a highly diverged Cas9 found in Listeria (similar to SauCas9) and Type II-C Cas9s, likely due to Cas9 HNH domain conservation. In summary, Listeria phages inactivate Cas9 in lytic growth using variable, narrow-spectrum inhibitors, while the broad-spectrum AcrIIA1 stimulates Cas9 degradation for protection of the lysogenic genome.
journal_name
Cell Host Microbejournal_title
Cell host & microbeauthors
Osuna BA,Karambelkar S,Mahendra C,Christie KA,Garcia B,Davidson AR,Kleinstiver BP,Kilcher S,Bondy-Denomy Jdoi
10.1016/j.chom.2020.04.001subject
Has Abstractpub_date
2020-07-08 00:00:00pages
31-40.e9issue
1eissn
1931-3128issn
1934-6069pii
S1931-3128(20)30190-6journal_volume
28pub_type
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