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The Bacteriophage EF-P29 Efficiently Protects against Lethal Vancomycin-Resistant Enterococcus faecalis and
Mengjun Cheng1, Jiaming Liang2, Yufeng Zhang1
1Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin UniversityChangchun, China.
Abstract:
Enterococcus faecalis is becoming an increasingly important opportunistic pathogen worldwide, especially because it can cause life-threatening nosocomial infections. Treating E. faecalis infections has become increasingly difficult because of the prevalence of multidrug-resistant E. faecalis strains. Because bacteriophages show specificity for their bacterial hosts, there has been a growth in interest in using phage therapies to combat the rising incidence of multidrug-resistant bacterial infections. In this study, we isolated a new lytic phage, EF-P29, which showed high efficiency and a broad host range against E. faecalis strains, including vancomycin-resistant strains. The EF-P29 genome contains 58,984 bp (39.97% G+C), including 101 open reading frames, and lacks known putative virulence factors, integration-related proteins or antibiotic resistance determinants. In murine experiments, the administration of a single intraperitoneal injection of EF-P29 (4 × 105 PFU) at 1 h after challenge was sufficient to protect all mice against bacteremia caused by infection with a vancomycin-resistant E. faecalis strain (2 × 109 CFU/mouse). E. faecalis colony counts were more quickly eliminated in the blood of EF-P29-protected mice than in unprotected mice. We also found that exogenous E. faecalis challenge resulted in enrichment of members of the genus Enterococcus (family Enterococcaceae) in the guts of the mice, suggesting that it can enter the gut and colonize there. The phage EF-P29 reduced the number of colonies of genus Enterococcus and alleviated the gut microbiota imbalance that was caused by E. faecalis challenge. These data indicate that the phage EF-P29 shows great potential as a therapeutic treatment for systemic VREF infection. Thus, phage therapies that are aimed at treating opportunistic pathogens are also feasible. The dose of phage should be controlled and used at the appropriate level to avoid causing imbalance in the gut microbiota.
Insights
A novel lytic bacteriophage, EF-P29, effectively combats multidrug-resistant Enterococcus faecalis infections. This phage therapy shows promise for treating vancomycin-resistant E. faecalis bacteremia and restoring gut microbiota balance in mice.
Area of Science:
- Microbiology
- Bacteriophage Therapy
- Infectious Diseases
Background:
- Enterococcus faecalis is a significant opportunistic pathogen causing life-threatening nosocomial infections.
- The rise of multidrug-resistant strains necessitates alternative treatment strategies.
- Bacteriophages offer a specific and promising approach to combat resistant bacterial infections.
Purpose of the Study:
- To isolate and characterize a novel lytic bacteriophage effective against Enterococcus faecalis.
- To evaluate the therapeutic potential of the isolated phage against vancomycin-resistant E. faecalis infections in a murine model.
- To assess the impact of phage therapy on gut microbiota composition during E. faecalis infection.
Main Methods:
- Isolation and characterization of a lytic bacteriophage, EF-P29, targeting Enterococcus faecalis.
- Genomic analysis of the EF-P29 phage to identify potential virulence or resistance factors.
- In vivo efficacy study in a murine model of vancomycin-resistant E. faecalis bacteremia.
- Analysis of gut microbiota composition using 16S rRNA sequencing.
Main Results:
- EF-P29 demonstrated high efficiency and a broad host range against E. faecalis, including vancomycin-resistant strains.
- The phage genome lacks known virulence factors, integration proteins, or antibiotic resistance determinants.
- A single dose of EF-P29 protected mice against lethal bacteremia and accelerated bacterial clearance.
- EF-P29 treatment reduced Enterococcus colonization and alleviated gut dysbiosis induced by E. faecalis.
Conclusions:
- The lytic phage EF-P29 is a potent therapeutic candidate for systemic vancomycin-resistant Enterococcus faecalis infections.
- Phage therapy is a feasible strategy for treating infections caused by opportunistic pathogens.
- Careful control of phage dosage is crucial to prevent gut microbiota imbalance.
