Characterization and Functional Studies of a Novel Depolymerase Against K19-Type Klebsiella pneumoniae

Yunfen Hua; Yongqin Wu; Minjie Guo; Ruijing Ma; Qingchuan Li; Zheyuan Hu; Hongrui Chen; Xingyu Zhang; Hui Li; Qingtian Li; Ping He

doi:10.3389/fmicb.2022.878800

Characterization and Functional Studies of a Novel Depolymerase Against K19-Type Klebsiella pneumoniae

Front Microbiol. 2022 Jun 22:13:878800. doi: 10.3389/fmicb.2022.878800. eCollection 2022.

Authors

Yunfen Hua^{1

2}, Yongqin Wu^{1

2}, Minjie Guo³, Ruijing Ma^{2

4}, Qingchuan Li², Zheyuan Hu², Hongrui Chen², Xingyu Zhang², Hui Li⁵, Qingtian Li⁵, Ping He^{2

4}

Affiliations

¹ College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China.
² Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Department of Nanoengineering, University of California, San Diego, La Jolla, CA, United States.
⁴ NHC Key Laboratory of Parasite and Vector Biology, National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China.
⁵ Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP), a pathogen that causes severe nosocomial infections and yields a high mortality rate, poses a serious threat to global public health due to its high antimicrobial resistance. Bacteriophages encode polysaccharide-degrading enzymes referred to as depolymerases that cleave the capsular polysaccharide (CPS), one of the main virulence factors of K. pneumoniae. In this study, we identified and characterized a new capsule depolymerase K19-Dpo41 from K. pneumoniae bacteriophage SH-KP156570. Our characterization of K19-Dpo41 demonstrated that this depolymerase showed specific activities against K19-type K. pneumoniae. K19-Dpo41-mediated treatments promoted the sensitivity of a multidrug-resistant K19-type K. pneumoniae strain to the bactericidal effect of human serum and significantly increased the survival rate of Galleria mellonella infected with K19-type K. pneumoniae. Our results provided strong primary evidence that K19-Dpo41 was not only effective in capsular typing of K19-type K. pneumoniae but promising in terms of developing new alternative therapeutic strategies against K19-type CRKP infections in the future.

Keywords: anti-infection of CRKP; bacteriophage; capsular typing; carbapenem-resistant Klebsiella pneumoniae; depolymerase.