Phage induction of Staphylococcus aureus pathogenicity islands promotes the CRISPR-Cas adaptive immune response

Staphylococcus aureus pathogenicity islands (SaPIs) are mobile genetic elements carrying virulence genes that contribute to the pathogenesis of this organism and spread upon infection by helper phages that induce their transfer. Staphylococci also carry type II and III CRISPR-Cas systems that mount an adaptive immune response against phages through the acquisition of spacer sequences from viral genomes that direct Cas nucleases to their targets. Whether and how SaPIs and CRISPR interact with each other during helper phage infection is not known. Here we report that, as a result of the packaging of incomplete helper phage genomes into SaPI particles that occurs during induction, defective viral DNA is delivered into new hosts that in turn stimulates spacer acquisition in both CRISPR types. Once immunized, staphylococci target the helper phage, prevent SaPI mobilization and favor the retention of the island within hosts. Our work reveals an unexpected synergy between CRISPR-Cas systems and SaPIs that enhance antiphage immunity and could favor the retention of beneficial elements within the population.