Recombination between phages and CRISPR-cas loci facilitates horizontal gene transfer in staphylococci.

Abstract

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) loci and their associated (cas) genes encode an adaptive immune system that protects prokaryotes from viral1 and plasmid2 invaders. Upon viral (phage) infection, a small fraction of the prokaryotic cells are able to integrate a small sequence of the invader’s genome into the CRISPR array1. These sequences, known as spacers, are transcribed and processed into small CRISPR RNA (crRNA) guides3–5 that associate with Cas nucleases to specify a viral target for destruction6–9. Although, CRISPR-cas loci are widely distributed throughout microbial genomes and often display hallmarks of horizontal gene transfer10–12, the drivers of CRISPR dissemination remain unclear. Here we show that spacers can recombine with phage target sequences to mediate a form of specialized transduction of CRISPR elements. Phage targets in phage 85, ΦNM1, ΦNM4, and Φ12 can recombine with spacers in either chromosomal or plasmid-borne CRISPR loci in Staphylococcus, leading to either the transfer of CRISPR-adjacent genes or the propagation of acquired immunity to other bacteria in the population, respectively. Our data demonstrate that spacer sequences not only specify the targets of Cas nucleases, but also can promote horizontal gene transfer.