Anti-CRISPRs go viral: The infection biology of CRISPR-Cas inhibitors

Bacteriophages encode diverse anti-CRISPR (Acr) proteins that inhibit CRISPR-Cas immunity during infection of their bacterial hosts. Although detailed mechanisms have been characterized for multiple Acr proteins, an understanding of their role in infection biology is just emerging. Here, we review recent work in this area and propose a framework of phage to evaluate CRISPR-immune evasion strategies. During infection, Acr proteins are deployed by a tightly regulated fast on-fast off transcriptional burst, which is necessary, but insufficient, for CRISPR-Cas inactivation. Instead of a single shutting down CRISPR-Cas immunity, a community of acr-carrying phages cooperate to suppress bacterial immunity, displaying low autonomy. Enzymatic Acr proteins with novel mechanisms have been recently revealed and are predicted to enhance autonomy, while DNA protective measures offer the highest autonomy observed. These varied Acr mechanisms and strengths also have unexpected impacts on the bacterial populations and competing phages.