Fig. 6: Functional consequences of CRISPR.

A Contour plot of the permanence of phage DNA in the cytoplasm of infected bacteria according to Model 2. Different shades of gray indicate the time needed for nucleases to remove the phage DNA from the cytoplasm of an infected bacterial cell (lighter colors indicate a faster elimination of phage DNA) Higher rates of DNA replication and cleavage reduce the time needed by nucleases to eliminate the phage DNA. The black region corresponds to slow phages that evade the action of nucleases. We hypothesize that the time it takes for nucleases to remove phage DNA from the cytoplasm of an infected bacterial cell provides a mechanistic criterion to include new phages in the CRISPR library. The late activation of the Cas enzymes (indicated by the red line) would constrain the creation of new spacers against susceptible phages as shown in B. The phage DNA would only be available for these enzymes in the region that corresponds to slow phages. B Some susceptible phages would be eliminated from the cytoplasm of the host cell before the formation of Ca1-Cas2 complexes (indicated by the red line). Fast phages, on the other hand, would kill the cell before the activation of the Cas enzymes. During infections by slow phages, Cas1-Cas2 would have enough time to create new spacers and therefore include the infecting phage in the CRISPR array of the infected cell (orange region). The creation of CRISPR spacers against very slow phages would not suffice to control the infection (gray region). C Reinfections of bacterial cells by phages that have changed their rates of DNA cleavage have three possible outcomes: the host cell can eliminate the phage (blue circle), it can create a new spacer against the same phage (black circle), it can be killed by the phage (white circle). If the rate of phage DNA destruction has not changed, then the immune memory of the bacterial cell suffices to neutralize the reinfection (red circle). D Contour plot of the permanence of phage DNA in the cytoplasm of infected bacteria according to Model 3. Lighter shades of gray indicate shorter permanence time of the phage DNA in the cytoplasm of the bacterial cell. The red line indicates the time of Cas enzymes activation. The action of CRISPR nucleases accelerates the degradation of the phage DNA (see (A) for comparison). This implies that the Cas enzymes cannot create new spacers in case of reinfection unless the rate of phage DNA has decreased since previous infections. The details of the simulations are provided in the “Methods” section.