Sixty percent of phage genomes of a size above 20 kb harbor genes for homologous recombination. These genes code for recombinases belonging to three different families, RecA-like, Rad52-like, and Gp2.5-like (Lopes et al., 2010). This abundance is surprising, since bacteria in which these phages propagate all provide a RecA activity that should suffice for the proceeding of the phage cycle. We have shown earlier that compared to RecA, Red beta, RecT and Erf (Rad52 super-family) are more efficient on small regions of homology, and when the DNA segments exchanged are not strictly identical. Due to this high activity, temperate phages encoding such recombinases capture genes from defective prophages present in the host in which they multiply (De Paepe et al., 2014).
We investigated whether this observation was also true for the Sak4 recombinase of the RecA-like family. We found that sak4 of HK620 (infecting Escherichia coli) has recombineering activity and requires an SSB-like accessory protein for full activity. Similar to Red beta, Sak4 recombines oligonucleotides with up to 12% of mismatches, relative to the chromosomal target gene. This ability of various phage recombinases encoded by temperate phages to perform exchanges between diverged sequences may explain their mosaic structure.
Phages used for therapy are virulent, and usually do not have temperate “relatives”. This way, the risk that a phage evolves by relaxed recombination during its lytic cycle is low, as the bacterial hosts should not contain related prophage sequences with which to recombine. However, in bacterial species where virulent phages are difficult to isolate, a strategy consists in selecting lytic mutants of temperate phages, having lost the function of their lysogeny module. Our studies predict that such lytic phages, if they encode a recombinase gene, could engage into genetic exchanges with their host at high pace.