CRISPR Immunity Drives Rapid Phage Genome Evolution in Streptococcus thermophilus

Phages remain an enigmatic part of the biosphere. As predators, they challenge the survival of host bacteria and archaea and set off an "arms race" involving host immunization countered by phage mutation. The CRISPR-Cas system is adaptive: by capturing fragments of a phage genome upon exposure, the host is positioned to counteract future infections. To investigate this process, we initiated massive deep-sequencing experiments with a host and infective phage and tracked the coevolution of both populations over hundreds of days. In the present study, we found that CRISPR immunity drives the accumulation of phage genome rearrangements (which enable longer phage survival) and escape mutations, establishing CRISPR as one of the fundamental drivers of phage evolution.