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A New Endolysin Lys59: A Broad-Spectrum Phage Endolysin Targeting Both Gram-Negative and Gram-Positive Bacteria
Yunhan Zhang1, Chenwei Deng1, Yanni Liu1
1College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
A novel phage-derived endolysin, Lys59, shows potent bactericidal activity against multidrug-resistant Klebsiella pneumoniae. This endolysin also demonstrates broad-spectrum efficacy and stability, highlighting its potential as an antibacterial agent.
Area of Science:
- Microbiology
- Structural Biology
- Biochemistry
Background:
- The rise of multidrug-resistant bacteria, particularly Klebsiella pneumoniae, poses a significant global health threat.
- Bacteriophage-derived endolysins are emerging as promising alternatives to conventional antibiotics due to their specific lytic activity.
Purpose of the Study:
- To characterize the antibacterial properties and structural features of the endolysin Lys59 from phage VB_KpP_HS106.
- To evaluate Lys59's efficacy against Klebsiella pneumoniae and its potential as a therapeutic agent.
Main Methods:
- Expression and purification of endolysin Lys59.
- In vitro antibacterial assays against Klebsiella pneumoniae and other bacterial strains.
- Structural analysis using molecular modeling and docking.
- Stability assays across various pH and temperature conditions.
- Biofilm inhibition assays.
Main Results:
- Lys59 demonstrated significant bactericidal activity against Klebsiella pneumoniae, achieving a 4 log reduction at 50 µg/mL within 2 hours.
- The endolysin exhibited broad-spectrum activity against both Gram-negative and Gram-positive bacteria.
- Lys59 maintained high activity across a pH range of 3-9 and temperatures from 4-55 °C.
- Metal ions differentially regulated Lys59 activity: K+ enhanced stability, while Mg2+ and Ca2+ inhibited function.
- Lys59 treatment reduced Klebsiella pneumoniae biofilm biomass by 44.6%.
Conclusions:
- The endolysin Lys59 possesses potent, broad-spectrum antimicrobial activity and favorable stability characteristics.
- Metal ion regulation of Lys59 activity provides insights for optimizing its therapeutic application.
- Lys59 shows significant potential as an antibacterial agent to combat multidrug-resistant Klebsiella pneumoniae infections and biofilms.
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