CRISPR systems provide transient immunity against phages

Bacteria and Archaea insert sequences (spacers) from viruses and other parasitic DNA into CRISPR loci to provide sequence-specific immunity. This can lead to rapid diversification and expansion of CRISPR loci over long timescales, yet most CRISPR arrays contain relatively few spacers. Using Pseudomonas aeruginosa PA14 and its phage DMS3vir as a model, we show that this is because spacer diversity is lost once the infectious phage has been driven extinct. As a result, CRISPR-Cas immune systems provide only a transient benefit to bacterial populations, which rapidly become unable to clear the same phage upon reinfection. Previously CRISPR dominated populations are replaced by either a spacer-lacking phage-sensitive genotype or a surface-resistant genotype carrying mutations in the pilus receptor gene . These results challenge the view that CRISPR loci accumulate resistance for trans-generational protection and help to explain why even highly active CRISPR loci have finite sizes.