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

## TL;DR

Staphylococcus aureus uses CRISPR-Cas systems to gain immunity against phages by acquiring spacers from defective viral DNA delivered by SaPIs.

## Contribution

The study reveals a synergy between CRISPR-Cas systems and SaPIs that enhances antiphage immunity through defective phage DNA.

## Key findings

- Defective phage DNA delivered by SaPIs stimulates CRISPR spacer acquisition in staphylococci.
- CRISPR-immunized staphylococci target helper phages and prevent SaPI mobilization.

## Abstract

Staphylococcus aureus pathogenicity islands (SaPIs) are mobile genetic elements carrying virulence genes that 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, directing 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, defective viral DNA delivered into new hosts stimulates spacer acquisition in both CRISPR types. Once immunized, staphylococci target the helper phage and prevent SaPI mobilization. Our work reveals an unexpected synergy between CRISPR-Cas systems and SaPIs that enhances antiphage immunity and could favor the retention of beneficial elements within the population.

Banh et al. show that staphylococci carrying CRISPR-Cas systems and SaPIs display enhanced rates of CRISPR spacer acquisition from phages. This requires delivery of incomplete, non-replicating phage genomes by SaPIs, which, as opposed to fully infective phages that rapidly kill the cell, allows CRISPR immunization of the host before its lysis.