Research progress of phage anti-CRISPR proteins

The CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated) system, an adaptive immune mechanism in bacteria and archaea, plays a crucial role in defense against phage and plasmid invasion. However, as the main natural enemies of bacteria, bacteriophages have evolved new mechanisms to escape host defenses through rapid mutation and diversification strategies. In response to the CRISPR-Cas system, phages have evolved proteins to inhibit the CRISPR-Cas system, thus revealing the complex evolutionary “arms race” between bacteriophages and their hosts. The study of anti-CRISPR (Acr) proteins offers novel insights into the molecular mechanisms of the CRISPR-Cas system and its potential applications in the precise regulation of gene editing and phage therapy. Consequently, a more profound comprehension of the anti-CRISPR system holds immense potential in numerous research domains. This review systematically summarizes the inhibitory mechanisms of anti-CRISPR proteins, highlights emerging applications, and proposes innovative directions to advance anti-CRISPR research.