Streptococcus thermophilus infected with lytic phage 2972

Many bacteria rely on CRISPR-Cas systems to provide adaptive immunity against phage, predation by which can shape the ecology and functioning of microbial communities. To characterize the impact of CRISPR immunization on phage genome evolution we performed long-term bacteria-phage (Streptococcus thermophilus – phage 2972) co-evolution experiments. We show that in this species CRISPR immunity drives fixation of single nucleotide polymorphisms that accumulate exclusively in phage genome regions targeted by CRISPR. Mutation rates in phage genomes highly exceed those of the host. The presence of multiple phage increased phage persistence by enabling recombination-based formation of chimeric phage genomes in which sequences heavily targeted by CRISPR are replaced. Collectively, results establish CRISPR-Cas adaptive immunity as a key driver of phage genome evolution under the conditions studied and highlight the importance of multiple co-existing phage for persistence in natural systems.