Bacteria and archaea can use the CRISPR-Cas system to recall past viral infections and mount targeted immune defenses against specific viral threats. Such bacterial immune memory depends on the number of spacers, or snippets of viral DNA stored in CRISPR cassettes and used by CRISPR-Cas to identify and clear recurring viral threats.

The researchers developed a statistical method to quantify trade-offs involved in the CRISPR-based adaptive immune system. Prokaryotes have been found to have a few dozen to a few hundred spacers, but given the potentially large size of bacterial genomes, it is unclear why relatively little genomic space is devoted to antiviral adaptive immune defense.

The authors found that the optimal size of the bacterial immune repertoire depends on the interplay between phage diversity and the number of Cas complexes present. With a very diverse viral landscape, as expected in nature, the size of the immune repertoire stored in CRISPR cassettes is constrained by the number of Cas complexes that the bacteria can mobilize to mount a functional immune response.

The model predicted that the optimal range of expressed spacers would lie between 10 and 100, consistent with observations. Thus, the study identifies a trade-off between bacterial immune memory and the effectiveness of antiviral response, according to the authors.

https://www.pnas.org/content/early/2020/02/14/1903666117

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