Fig. 2: CRISPR and RM systems are widespread in S. thermophilus, and phages have several counter defense mechanisms.

Co-occurrence of (A). CRISPR-Cas loci and (B). RM types within the same S. thermophilus genome. C Distribution of the number of RM systems per genome according to the type. D Heatmap of co-occurrence within the same genome of RM type II with different predicted restriction sites. Only strains harboring at least two RM type II systems are shown on the phylogenetic tree (N = 95). RM systems with no predicted restriction site were divided into different unknown categories based on the restriction enzyme annotation (MvaII or AlwI) or subtype (IIG). E Prevalence of predicted anti-CRISPR (ACR) proteins in phages infecting S. thermophilus (N = 191, NCBI June 2023). Experimentally validated ACRs in S. thermophilus are marked with a star. Color coding corresponds to phage genus. F Plot of the ratios of observed to expected number of restriction sites in streptococcal phages for RM type II and III restriction sites (predicted with REBASE). The observed number of sites corresponds to the count of each site within the phage genomes, while the expected number was estimated using a Markov-immediate neighbor dependence statistical model⁶⁸. Ratios < 0.75 indicate underrepresentation and ratios > 1.25 indicate overrepresentation. Source data are provided as a Source Data file.