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Published on: January 7, 2019
Characterization and Therapeutic Potential of Three Depolymerases Against K54 Capsular-Type Klebsiella pneumoniae
Yanjun Lu1, Chengju Fang1, Li Xiang1
1The School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China.
Abstract:
Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp), a pathogen causing severe nosocomial infections and high mortality rates, is increasingly becoming a serious global public health threat. Capsular polysaccharide (CPS), a major virulence factor of hvKp, can be enzymatically degraded by bacteriophage-derived depolymerases. However, to our knowledge, depolymerases targeting K. pneumoniae K54-type strains have rarely been identified. Here, we identified and characterized three novel capsule depolymerases, Dep_C, Dep_Y, and Dep_Z, derived from three different K. pneumoniae phages, which retained robust activity across a broad pH range (pH 3.0-12.0) and demonstrated thermal stability up to 50 °C. These depolymerases could efficiently digest the CPS of K. pneumoniae K54-serotype strains, significantly inhibit biofilm formation, and remove their mature biofilms. Although no bactericidal activity was detected, these depolymerases rendered host bacteria susceptible to serum complement-mediated killing. We further demonstrate that Dep_C, Dep_Y, and Dep_Z can effectively and significantly prolong the survival time of mice in a pneumonia model infected with K54-type K. pneumoniae and reduce the colonization and virulence of the bacteria in the mice. These findings indicate that depolymerases Dep_C, Dep_Y, and Dep_Z could increase bacterial susceptibility to host immune responses of hvKp to the host through their degradation effect on the CPS. In conclusion, our study demonstrates that the three capsule depolymerases are promising antivirulent agents to combat CR-hvKp infections.
Insights
Three novel bacteriophage depolymerases effectively degrade the capsule of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp). These depolymerases inhibit biofilm formation and enhance bacterial susceptibility to host immune responses, offering a promising antivirulent strategy against CR-hvKp infections.
Area of Science:
- Microbiology
- Virology
- Infectious Diseases
Background:
- Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) is a significant threat causing severe hospital infections.
- Bacteriophage-derived depolymerases can degrade the capsular polysaccharide (CPS) of K. pneumoniae, a key virulence factor.
- Depolymerases targeting K. pneumoniae K54-type strains are scarce.
Purpose of the Study:
- To identify and characterize novel bacteriophage depolymerases targeting K. pneumoniae K54-type strains.
- To evaluate the efficacy of these depolymerases in inhibiting CR-hvKp virulence and biofilm formation.
- To assess the potential of these depolymerases as antivirulent agents against CR-hvKp infections.
Main Methods:
- Isolation and characterization of three novel capsule depolymerases (Dep_C, Dep_Y, Dep_Z) from K. pneumoniae phages.
- Assessment of depolymerase activity across a broad pH range and thermal stability.
- Evaluation of depolymerase efficacy in digesting K54-type CPS, inhibiting biofilm formation, and enhancing serum complement-mediated killing.
Main Results:
- Dep_C, Dep_Y, and Dep_Z showed robust activity across pH 3.0-12.0 and up to 50 °C.
- These depolymerases efficiently digested K54-type CPS, inhibited biofilm formation, and removed mature biofilms.
- Depolymerases increased bacterial susceptibility to serum killing and prolonged mouse survival in a pneumonia model, reducing bacterial colonization and virulence.
Conclusions:
- The novel depolymerases Dep_C, Dep_Y, and Dep_Z are effective against K. pneumoniae K54-type strains.
- These depolymerases enhance CR-hvKp susceptibility to host immune responses by degrading CPS.
- Depolymerases represent promising antivirulent agents for combating CR-hvKp infections.
