Bacteriophages avoid autoimmunity from cognate immune systems as an intrinsic part of their life cycles

Dormant prophages protect lysogenic cells by expressing diverse immune systems, which must avoid targeting their cognate prophages upon activation. Here, we report that multiple Staphylococcus aureus prophages encode Tha (Tail-activated, HEPN domain-containing Anti-phage system), a defence system activated by structural tail proteins of incoming phages. We demonstrate the function of two Tha systems, Tha-1 and Tha-2, activated by distinct tail proteins. Interestingly, Tha systems can also block reproduction of the induced tha-positive prophages. To prevent autoimmunity after prophage induction, these systems are inhibited by the product of a small overlapping antisense gene previously believed to encode an excisionase. This genetic organisation, conserved in S. aureus prophages, allows Tha systems to protect prophages and their bacterial hosts against phage predation, and be turned off during prophage induction, balancing immunity and autoimmunity. Our results demonstrate that the fine regulation of these processes is essential for the correct development of prophages' life cycle.The data in this bioproject relates to the RNAseq performed on 80a phage infection of S. aureus cells, tracking transcript abundances over time.