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Published on: May 4, 2018
LysZX4-NCA, a new endolysin with broad-spectrum antibacterial activity for topical treatment
Ping Li1, Mangmang Shen1, Wenjie Ma1
1College of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou 225009, PR China.
Abstract:
The prevalence of multidrug-resistant highly virulent Klebsiella pneumoniae (MDR-hvKP) requires the development of new therapeutic agents. Herein, a novel lytic phage vB_KpnS_ZX4 against MDR-hvKP was discovered in hospital sewage. Phage vB_KpnS_ZX4 had a short latent period (5 min) and a large burst size (230 PFU/cell). It can rapidly reduce the number of bacteria in vitro and improve survival rates of bacteremic mice in vivo from 0 to 80 % with a single injection of 108 PFU. LysZX4, an endolysin derived from vB_KpnS_ZX4, exhibits potent antimicrobial activity in vitro in combination with ethylenediaminetetraacetic acid (EDTA). The antimicrobial activity of LysZX4 was further enhanced by the fusion of KWKLFKI residues from cecropin A (LysZX4-NCA). In vitro antibacterial experiments showed that LysZX4-NCA exerts broad-spectrum antibacterial activity against clinical Gram-negative bacteria, including MDR-hvKP. Moreover, in the mouse model of MDR-hvKP skin infection, treatment with LysZX4-NCA resulted in a three-log reduction in bacterial burden on the skin compared to the control group. Therefore, the novel phages vB_KpnS_ZX4 and LysZX4-NCA are effective reagents for the treatment of systemic and local MDR-hvKP infections.
Insights
A novel phage and its derived endolysin show promise against multidrug-resistant Klebsiella pneumoniae. These agents effectively reduced bacterial loads in vitro and improved survival in mice with systemic and skin infections.
Area of Science:
- Microbiology
- Bacteriology
- Phage Therapy
Background:
- Multidrug-resistant highly virulent Klebsiella pneumoniae (MDR-hvKP) poses a significant threat, necessitating novel therapeutic strategies.
- Existing treatments are becoming less effective due to rising antimicrobial resistance.
Purpose of the Study:
- To discover and characterize a novel lytic bacteriophage effective against MDR-hvKP.
- To evaluate the therapeutic potential of the phage and its derived endolysin for treating MDR-hvKP infections.
Main Methods:
- Isolation and characterization of lytic phage vB_KpnS_ZX4 from hospital sewage.
- In vitro and in vivo efficacy studies of the phage and its endolysin (LysZX4-NCA) against MDR-hvKP.
- Assessment of LysZX4-NCA's broad-spectrum activity against Gram-negative bacteria.
Main Results:
- Phage vB_KpnS_ZX4 demonstrated a short latent period (5 min) and large burst size (230 PFU/cell).
- Single phage injection significantly improved survival rates in bacteremic mice (0% to 80%).
- LysZX4-NCA showed potent broad-spectrum activity, reducing bacterial burden in skin infection models by three logs.
Conclusions:
- The lytic phage vB_KpnS_ZX4 and its engineered endolysin LysZX4-NCA are promising candidates for treating MDR-hvKP infections.
- These agents offer potential therapeutic solutions for both systemic and localized MDR-hvKP infections.
