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Published on: April 18, 2019
Prophage-Derived Endolysin E1 Synergizes with Meropenem Against Acinetobacter baumannii.
Jinyu Wang1, Jinlong Bai1, Yuhui Li1
1College of Life Sciences, Shihezi University, Shihezi 832003, China.
New phage-derived endolysin E1 shows potent activity against carbapenem-resistant Acinetobacter baumannii (CRAB). Combination therapy with E1 and meropenem significantly improves survival rates in infection models.
Area of Science:
- Microbiology
- Biochemistry
- Infectious Diseases
Background:
- Carbapenem-resistant Acinetobacter baumannii (CRAB) is a critical priority pathogen requiring novel therapeutic strategies.
- Genomic mining identified numerous prophage-derived endolysin candidates for antimicrobial development.
Purpose of the Study:
- To identify and characterize novel endolysins with bactericidal activity against CRAB.
- To evaluate the efficacy of a promising endolysin, E1, as a monotherapy and in combination with meropenem.
Main Methods:
- Genomic analysis of 5144 prophage-derived endolysin candidates from 27,531 A. baumannii genomes.
- Recombinant expression and functional evaluation of four top candidates (E1-E4).
- In vitro assays for bactericidal activity, biofilm disruption, and stability; structural analysis; murine infection model.
Main Results:
- Endolysin E1 demonstrated potent bactericidal activity against CRAB strains (micromolar MIC) and disrupted biofilms.
- E1 exhibited stability across a wide range of temperatures, pH, and salt concentrations.
- Combination therapy of E1 and meropenem significantly increased survival (66.7%) and reduced bacterial loads in a murine model.
Conclusions:
- Prophage-derived endolysin E1 is a potent antimicrobial agent against A. baumannii.
- E1 exhibits synergistic activity with meropenem, highlighting its potential for combination therapies against CRAB infections.
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