Adsorption of phage T2 is inhibited due to inversion of cryptic prophage DNA by the serine recombinase PinQ

Recombinases catalyze site-specific integration, excision, and inversion of DNA and are often found adjacent to anti-phage system genes clustered in 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 PinQ (<ani:underline>P</ani:underline> segment <ani:underline>in</ani:underline>version by <ani:underline>Q</ani:underline>in) of Escherichia coli cryptic prophage Qin and discover that it inhibits T2 phage infection by inverting a 1797 bp segment in a different cryptic prophage e14; this inversion leads to the formation of a novel protein from two chimeric 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 PinQ anti-phage defense by mutating gp38 in the hypervariable region 3. Therefore, we discovered the first recombinase-activated phage inhibition system.