Non-canonical inhibition strategies and structural basis of anti-CRISPR proteins targeting type I CRISPR-Cas systems

Mobile genetic elements (MGEs) such as bacteriophages and their host prokaryotes are trapped in an eternal battle against each other. To cope with foreign infection, bacteria and archaea have evolved mul-tiple immune strategies, out of which CRISPR-Cas system is up to now the only discovered adaptive sys-tem in prokaryotes. Despite the fact that CRISPR-Cas system provides powerful and delicate protection against MGEs, MGEs have also evolved anti-CRISPR proteins (Acrs) to counteract the CRISPR-Cas immune defenses. To date, 46 families of Acrs targeting type I CRISPR-Cas system have been charac-terized, out of which structure information of 21 families have provided insights on their inhibition strate-gies. Here, we review the non-canonical inhibition strategies adopted by Acrs targeting type I CRISPR-Cas systems based on their structure information by incorporating the most recent advances in this field, and discuss our current understanding and future perspectives. The delicate interplay between type I CRISPR-Cas systems and their Acrs provides us with important insights into the ongoing fierce arms race between prokaryotic hosts and their predators. (c) 2023 Elsevier Ltd. All rights reserved.