Cell 178, 1452–1464 (2019).

It is now known that bacterial viruses (phages) can attain genes encoding anti-CRISPR (Acr) proteins to inhibit CRISPR systems. These Acr proteins exhibit large sequence diversity, yet it is often found that Acr genes are adjacent to genes encoding proteins containing a helix-turn-helix (HTH) DNA-binding motif. These anti-CRISPR-associated (Aca) genes have been considered as markers for identifying anti-CRISPR families. In spite of the wide presence of Aca genes, the functions of Aca proteins have not been carefully examined. Stanley et al. used a Pseudomonas phage, JBD30, as a model system to study the transcript levels of an Acr gene (AcrIF1) during an infection cycle. They uncovered that Aca proteins serve as a repressor of the Acr promoter, and can thus attenuate anti-CRISPR transcription. In the absence of Aca activity, the strong transcription of Acr genes is detrimental for phage survival. These findings of inhibiting anti-CRISPR systems may add a new tuning knob for CRISPR-based genome-editing tools.