A Novel Polysaccharide Depolymerase Encoded by the Phage SH-KP152226 Confers Specific Activity Against Multidrug-Resistant Klebsiella pneumoniae via Biofilm Degradation

The increasing prevalence of infections caused by multidrug-resistant <i>Klebsiella pneumoniae</i> necessitates the development of alternative therapies. Here, we isolated, characterized, and sequenced a <i>K. pneumoniae</i> bacteriophage (SH-KP152226) that specifically infects and lyses <i>K. pneumoniae</i> capsular type K47. The phage SH-KP152226 contains a genome of 41,420 bp that encodes 48 predicted proteins. Among these proteins, Dep42, the gene product of ORF42, is a putative tail fiber protein and hypothetically possesses depolymerase activity. We demonstrated that recombinant Dep42 showed specific enzymatic activities in the depolymerization of the K47 capsule of <i>K. pneumoniae</i> and was able to significantly inhibit biofilm formation and/or degrade formed biofilms. We also showed that Dep42 could enhance polymyxin activity against <i>K. pneumoniae</i> biofilms when used in combination with antibiotics. These results suggest that combination of the identified novel depolymerase Dep42, encoded by the phage SH-KP152226, with antibiotics may represent a promising strategy to combat infections caused by drug-resistant and biofilm-forming <i>K. pneumoniae</i>.