Identification of New Anti-CRISPRs Uncovers Anti-Defense Gene Clustering

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology; University of California, San Francisco (UCSF) - Quantitative Biosciences Institute

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Abstract

Many prokaryotes employ CRISPR-Cas systems to combat invading mobile genetic elements (MGEs). In response, MGEs have evolved Anti-CRISPR (Acr) proteins to bypass this immunity. Here, we describe the analysis of gene neighbors of the anti-CRISPR associated gene 5 (aca5) in search of new Acrs on chromosomal and extrachromosomal MGEs. Functional testing of candidates was performed against a panel of six type I systems, revealing 11 type I-F and/or I-E Acrs and a new aca (aca9). We find that acr genes not only associate with other acr genes, but also with inhibitors of distinct bacterial defense systems. These genomic regions appear to be “anti-defense islands”, reminiscent of the clustered arrangement of “defense islands” in prokaryotic genomes. Our findings expand on the diversity of CRISPR-Cas inhibitors and reveal the potential exploitation of acr loci neighborhoods for identifying new anti-defense systems.

Keywords: CRISPR-Cas, Phages, Anti-CRISPR, molecular microbiology, Horizontal gene transfer, mobile genetic elements, plasmids, conjugative element, defense systems, bacterial immunity, defense island, anti-defense island

Suggested Citation: Suggested Citation

Pinilla-Redondo, Rafael and Shehreen, Saadlee and D. Marino, Nicole and D. Fagerlund, Robert and M. Brown, Chris and Soerensen, Soren J. and C. Fineran, Peter and Bondy-Denomy, Joseph, Identification of New Anti-CRISPRs Uncovers Anti-Defense Gene Clustering. Available at SSRN: https://ssrn.com/abstract=3575655 or http://dx.doi.org/10.2139/ssrn.3575655

This version of the paper has not been formally peer reviewed.