Isolation and Characterization of Two Phages Encoding Divergent Depolymerases.

The emergence of multidrug-resistant bacteria is a major global health concern. The search for new therapies has brought bacteriophages into the spotlight, and new phages are being described as possible therapeutic agents. Among the bacteria that are most extensively resistant to current antibiotics is , whose hypervariable extracellular capsule makes treatment particularly difficult. Here, we describe two new phages, and , isolated from environmental samples. These phages belong to the genus within the family . Both phages encode a similar tail spike protein with putative depolymerase activity, which is shared among other related phages and probably determines their ability to specifically infect capsular types K22 and K37. In addition, we found that phage also infects capsular type K13 and is capable of striping the capsules of KL2 and KL3, although the phage was not infectious in these two strains. Genome sequence analysis suggested that the extended tropism of phage is conferred by a second, divergent depolymerase. Phage encodes yet another putative depolymerase, but we found no activity of this phage against capsular types other than K22 and K37, after testing a panel of 77 reference strains. Overall, our results confirm that most phages productively infected one or few capsular types. This constitutes an important challenge for clinical applications.