Target discrimination by bacterial immune systems

Temperate phages that integrate into the bacterial genome can carry genes that confer a fitness advantage. However, it has been unclear how this potential beneficial interaction is balanced against host defence by CRISPR-Cas immune systems, which defend bacteria against phage infection using Cas nucleases and small RNA guides that provide sequence specificity for cleavage of target sites in the phage genome. Here Luciano Marraffini and colleagues show that the Staphylococcus epidermidis CRISPR-Cas system can prevent lytic phage infection but tolerate lysogenization by temperate phage through a transcription-dependent DNA targeting mechanism. This work expands the repertoire of CRISPR-based immune functions to include a facility for conditional tolerance of foreign elements.