Lysogeny is one major reason why bacteria have been spared from extinction caused by phages. Bacteria also have their own defenses against phages. First, natural selection favors bacterial mutants with surface proteins that are no longer recognized as receptors by a particular type of phage. Second, when phage DNA does enter a bacterium, the DNA often is identified as foreign and cut up by cellular enzymes called restriction enzymes, which are so named because they restrict a phage’s ability to replicate within the bacterium. The bacterium’s own DNA is methylated in a way that prevents attack by its own restriction enzymes. A third defense is a system present in both bacteria and archaea called the CRISPR-Cas system.
The CRISPR-Cas system was discovered during a study of repetitive DNA sequences present in the genomes of many prokaryotes. These sequences, which puzzled scientists, were named clustered regularly interspaced short palindromic repeats (CRISPRs) because each sequence read the same forward and backward (a palindrome), with different stretches of “spacer DNA” in between the repeats. At first, scientists assumed the spacer DNA sequences were random and meaningless, but analysis by several research groups showed that each spacer sequence corresponded to DNA from a particular phage that had infected the cell. Further studies revealed that particular nuclease proteins interact with the CRISPR region. These nucleases, called Cas (CRISPR-associated) proteins, can identify and cut phage DNA, thereby defending the bacterium against phage infection.
When a phage infects a bacterial cell that has the CRISPR-Cas system, the DNA of the invading phage is integrated into the genome between two repeat sequences. If the cell survives the infection, any further attempt by the same type of phage to infect this cell (or its offspring) triggers transcription of the CRISPR region into RNA molecules. These RNAs are cut into pieces and then bound by Cas proteins. The Cas protein uses a portion of the phage-related RNA as a homing device to identify the invading phage DNA and cut it, leading to its destruction.
Just as natural selection favors bacteria that have receptors altered by mutation or that have enzymes that cut phage DNA, it also favors phage mutants that can bind to altered receptors or that are resistant to enzymes. Thus, the bacterium-phage relationship is in constant evolutionary flux.
Urry, Lisa A.. Campbell Biology (p. 401). Pearson Education. Kindle Edition.