The arms race between bacteria and phages led to the development of sophisticated anti-
phage defense systems, including CRISPR-Cas and restriction-modification systems. To
identify additional unknown defense systems in microbial genome we systematically
examined gene families that are clustered next to known defense systems in bacterial and
archaeal “Defense Islands”. Candidate systems were cloned into model bacteria and their
effect on phage susceptibility was tested against a wide array of phages. Nine new anti-
phage defense systems were identified. In addition, a system providing protection against
plasmid transformation was also detected.