Targeting of temperate phages drives loss of type I CRISPR-Cas systems

Upon infection of their host, temperate phages (viruses that infect bacteria) enter either a lytic or a lysogenic cycle. The former results in bacterial cell lysis and phage release (horizontal transmission), while lysogeny is characterized by integration of the phage in the host genome and dormancy (vertical transmission)(1). Co-culture experiments of bacteria and temperate phage mutants, which are locked in the lytic cycle, have shown that CRISPR-Cas can efficiently eliminate the invading phages(2,3). By contrast, here we show that when challenged with wild-type temperate phage that can become lysogenic, type I CRISPR-Cas immune systems are unable to eliminate these phages from the bacterial population. In fact, our data suggest that CRISPR-Cas immune systems are in this context maladaptive to the host due to severe immunopathological effects brought about by imperfect matching of spacers to integrated phage sequences (prophages). These fitness costs drive the loss of CRISPR-Cas from bacterial populations, unless the phage carries anti-CRISPR (acr) genes that suppress the immune system of the host. Using bioinformatics, we show that this imperfect targeting is likely to occur frequently in nature. These findings can help to explain the patchy distribution of CRISPR-Cas immune systems within and between bacterial species and highlight the strong selective benefits of phage-encoded acr genes for both the phage and host under these circumstances.