Adaptation in bacterial CRISPR-Cas immunity can be driven by defective phages

Clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated cas genes serve as a prokaryotic ‘adaptive’ immune system, protecting against foreign DNA elements such as bacteriophages. CRISPR-Cas systems function by incorporating short DNA ‘spacers’, homologous to invading DNA sequences, into a CRISPR array (adaptation). The array is then transcribed and matured into RNA molecules (maturation) that target homologous DNA for cleavage (interference). It is unclear how these three stages could occur quickly enough in a naive phage-infected cell to interfere with phage replication before this cell would be irrevocably damaged by the infection. Here we demonstrate that cells can acquire spacers from defective phages at a rate directly proportional to the quantity of replication-deficient phages to which the cells are exposed. This process is reminiscent of immunization in humans by vaccination with inactivated viruses.