One trick of bacteriophage to evade destroy by its host

What is it about?

Phages are the viruses of bacterial hosts. In the arms race between them, diverse defense systems have been evolved by the hosts to destroy the invading phages, among which CRISPR-Cas system is famous due to its broad application in gene editing. To survive, phages have evolved anti-CRISPR proteins to prevent the cleavage of their genomes by CRISPR-Cas systems. This article elucidates the mechanism of one anti-CRISPR protein named AcrIIC4, which can inhibit Cas9 cleavage. In this study, we captured a series of snapshots of Cas9 in the presence or absence of AcrIIC4 and uncovered its action mechanism using biophysical and biochemical methods. Without AcrIIC4, Cas9 formed surveillance complex with CRISPR-RNA, which can recognize the DNA from phages and break it down to fragments. During this process, Cas9 movement and formation of a structure named R-loop are essential. In contrast, in the presence of AcrIIC4, AcrIIC4 will lock one part of Cas9 protein responsible for DNA recognition, preventing R-loop formation. As a result, Cas9 cannot cleave the phage DNA anymore.

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Photo by CDC on Unsplash

Photo by CDC on Unsplash

Why is it important?

Phages are the most abundant entity on the earth. Understanding the relationship between phages and their hosts is valuable for the maintenance of a healthy ecosystem. Moreover, Cas9 is the sharpest scissor for gene-editing application, and anti-CRISPR proteins like AcrIIC4 hold the potential to be developed as regulation tools of Cas9. The elucidation of the molecular mechanism of AcrIIC4 will enrich the toolkits of genome editing.

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