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

Yunqiang Wu; Rui Wang; Mengsha Xu; Yanan Liu; Xianchao Zhu; Jiangfeng Qiu; Qiming Liu; Ping He; Qingtian Li

doi:10.3389/fmicb.2019.02768

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

Front Microbiol. 2019 Dec 3:10:2768. doi: 10.3389/fmicb.2019.02768. eCollection 2019.

Authors

Yunqiang Wu¹, Rui Wang², Mengsha Xu³, Yanan Liu¹, Xianchao Zhu⁴, Jiangfeng Qiu², Qiming Liu³, Ping He³, Qingtian Li¹

Affiliations

¹ Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Research, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Department of Gastrointestinal Surgery, Shanghai Ruizhou Biotech Co. Ltd., Shanghai, China.

Abstract

The increasing prevalence of infections caused by multidrug-resistant Klebsiella pneumoniae necessitates the development of alternative therapies. Here, we isolated, characterized, and sequenced a K. pneumoniae bacteriophage (SH-KP152226) that specifically infects and lyses K. pneumoniae 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 K. pneumoniae and was able to significantly inhibit biofilm formation and/or degrade formed biofilms. We also showed that Dep42 could enhance polymyxin activity against K. pneumoniae 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 K. pneumoniae.

Keywords: bacteriophage; biofilm; capsular polysaccharide; carbapenem-resistant Klebsiella pneumoniae; depolymerase.