Cas10 relieves host growth arrest to facilitate spacer retention during type III-A CRISPR-Cas immunity.

Cells from all kingdoms of life can enter growth arrest in unfavorable environmental conditions. Key to this process are mechanisms enabling recovery from this state. Staphylococcal type III-A CRISPR-Cas loci encode the Cas10 complex that uses a guide RNA to locate complementary viral transcripts and start an immune response. When the target sequence is expressed late in the viral lytic cycle, defense requires the activity of Csm6, a non-specific RNase that inhibits the growth of the infected cell. How Csm6 protects from infection and whether growth can be restored is not known. Here, we show that growth arrest provides immunity at the population level, preventing viral replication and allowing uninfected cells to propagate. In addition, the ssDNase activity of Cas10 is required for the regrowth of a subset of the arrested cells and the recovery of the infected host, presumably ending the immune response through degradation of the viral DNA.