Serine Recombinase PinR Inverts Cryptic Prophage DNA to Block Adsorption of Phages

Recombinases catalyze site-specific integration, excision, and inversion of DNA and are found in myriad defense islands; however, their function in phage-defense is unknown as they are frequently dismissed as markers of prophages. Here, we characterize the physiological role of the previously-uncharacterized serine recombinase PinR of Escherichia coli cryptic prophage rac and discover that it inhibits T2 phage infection by inverting a 1,797 bp segment in a different cryptic prophage e14 to inhibit T2 infection; this inversion leads to the formation of a novel protein from two spliced genes, StfE2, that we find blocks phage adsorption. Modeling shows StfE2 inhibits T2 phage adsorption by preventing Gp38 binding to its primary receptors porins FadL and OmpF. Corroborating the receptor-blocking hypothesis, T2 escape mutants evolve resistance to PinR phage defense by mutating gp38 to remove 16 aa in the hyper variable region 3. Therefore, we discovered the first recombinase-activated phage inhibition system.