Abstract
Bacteriophages must rapidly deploy anti-CRISPR proteins (Acrs) to inactivate the RNA-guided nucleases that enforce CRISPR-Cas adaptive immunity in their bacterial hosts. Listeria monocytogenes temperate phages encode up to three anti-Cas9 proteins, with acrIIA1 always present. AcrIIA1 binds and inhibits Cas9 with its C-terminal domain; however, the function of its highly conserved N-terminal domain (NTD) is unknown. Here, we report that the AcrIIA1NTD is a critical transcriptional repressor of the strong anti-CRISPR promoter. A rapid burst of anti-CRISPR transcription occurs during phage infection and the subsequent negative feedback by AcrIIA1NTD is required for optimal phage replication, even in the absence of CRISPR-Cas immunity. In the presence of CRISPR-Cas immunity, full-length AcrIIA1 uses its two-domain architecture to act as a “Cas9 sensor,” tuning acr expression according to Cas9 levels. Finally, we identify AcrIIA1NTD homologs in other Firmicutes and demonstrate that they have been co-opted by hosts as “anti-anti-CRISPRs,” repressing phage anti-CRISPR deployment. Show more
Publication status
publishedExternal links
Journal / series
Cell Host & MicrobeVolume
Pages / Article No.
Publisher
Cell PressSubject
CRISPR-Cas; Cas9; Bacteriophage; anti-CRISPR; Listeria monocytogenes; Autorepression; Anti-anti-CRISPROrganisational unit
03651 - Loessner, Martin / Loessner, Martin
Funding
174108 - Synthetic Bacteriophage Platform for Diagnostics and Control of Drug-Resistant Pathogenic Bacteria (SNF)
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