Anti-CRISPR proteins inhibit CRISPR–Cas systems through various mechanisms. Each anti-CRISPR protein examined to date is associated with Pseudomonas aeruginosa and is encoded by an operon that also encodes a homologue of Aca1 or Aca2, which are putative transcriptional regulators. Pawluk et al. used a guilt-by-association approach to identify candidate anti-CRISPR genes located in proximity to aca1 and aca2 homologues. Five new families of anti-CRISPR proteins were identified, all of which were able to inhibit type I-F CRISPR–Cas systems in P. aeruginosa; however, the genes that encode these anti-CRISPR proteins were not restricted to Pseudomonas spp. but instead were widely distributed throughout the Proteobacteria. Thus, these anti-CRISPR proteins were able to promiscuously inhibit CRISPR–Cas systems from species other than their natural host. Finally, one anti-CRISPR protein had acquired a carboxy-terminal region that enabled the protein to inhibit type I-E CRISPR–Cas systems in addition to type I-F CRISPR–Cas systems.