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Published on: August 19, 2021
Phage vB_Kpn_HF0522: Isolation, Characterization, and Therapeutic Potential in Combatting K1 Klebsiella pneumoniae
Tao Yan1,2, Qiuyan Wang2, Chengcheng Ma2
1Department of Clinical Laboratory Center, Anhui Chest Hospital, Hefei, 230031, People's Republic of China.
Purpose:
Klebsiella pneumoniae is a globally prevalent pathogen responsible for severe hospital- and community-acquired infections, and presents significant challenges for clinical management. Current therapeutic strategies are no longer able to meet the clinical needs; therefore, there is an urgent need to develop novel therapeutic strategies. This study aimed to evaluate the efficacy of phage therapy in treating bacterial infections.
Methods:
Isolated phage vB_Kpn_HF0522 and phage morphology were observed using transmission electron microscopy. Analysis of vB_Kpn_HF0522 characteristics, including optimal multiplicity of infection (MOI), one-step growth curve, host range, stability in different environments, and adsorption capacity. The phage genomic sequence was analyzed to explore evolutionary relationships. The effect of phage vB_Kpn_HF0522 on biofilms was assessed using crystal violet staining assay. The Galleria mellonella (G. mellonella) infection model and mouse infection models were established to evaluate the practical application potential of the phage and the fitness cost of phage-resistant bacteria.
Results:
Phage was isolated from hospital sewage for experimental studies. Genome analysis revealed that vB_Kpn_HF0522 is a double-stranded linear DNA virus. Biological characterization demonstrated that this phage specifically targets serotype K1 K. pneumoniae with an optimal multiplicity of infection (MOI) of 0.01, effectively disrupting biofilms and inhibiting bacterial growth. The bacterial growth rate remained largely unchanged after the phage resistance mutation, but mice infected with the mutant strain showed significantly higher survival rates than those infected with the wild-type strain. vB_Kpn_HF0522 increased the survival rate of infected G. mellonella from 12.5% to 75%, inhibited incisional surgical site infections and alleviated inflammatory response in mice.
Conclusion:
These findings indicate that vB_Kpn_HF0522 has significant potential for treating specific bacterial infections, and may serve as an antimicrobial agent for research and clinical anti-infective therapy.
Insights
Phage therapy using vB_Kpn_HF0522 shows promise against Klebsiella pneumoniae infections. This novel antimicrobial agent effectively targets biofilms and reduces infection severity in animal models, offering a potential new treatment strategy.
Area of Science:
- Microbiology
- Virology
- Infectious Diseases
Background:
- Klebsiella pneumoniae is a major cause of severe hospital and community infections.
- Existing treatments for Klebsiella pneumoniae are becoming less effective.
- Novel therapeutic strategies are urgently needed to combat this pathogen.
Purpose of the Study:
- To evaluate the efficacy of phage therapy in treating Klebsiella pneumoniae infections.
- To characterize a novel bacteriophage, vB_Kpn_HF0522, for therapeutic potential.
Main Methods:
- Isolation and characterization of bacteriophage vB_Kpn_HF0522.
- Assessment of phage morphology, host range, stability, and adsorption.
- Genomic sequencing of the phage.
- Evaluation of phage efficacy against biofilms and in Galleria mellonella and mouse infection models.
Main Results:
- Phage vB_Kpn_HF0522 specifically targets serotype K1 Klebsiella pneumoniae.
- The phage effectively disrupts biofilms and inhibits bacterial growth.
- In vivo studies showed increased survival rates in infected Galleria mellonella and mice, with reduced infection and inflammation.
Conclusions:
- Bacteriophage vB_Kpn_HF0522 demonstrates significant potential as an antimicrobial agent.
- This phage can be a valuable tool for research and clinical anti-infective therapy against Klebsiella pneumoniae.
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