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Novel Enterococcus phage BUCT630: Isolation and genomic insights targeting drug-resistant Enterococcus faecium in
Zakir Ullah1, Rashid Ahmad1, Amna Shafqat1
1College of Life Sciences and Technology, Beijing University of Chemical Technology, Beijing, 100029, China.
Abstract:
The antibiotic-resistant Enterococcus faecium (E. faecium) is a significant health issue requiring alternative therapies. Phages could be an alternative to antibiotics and have promising activity in both in vitro and in vivo experiments. Here, we isolated and characterized a new lytic phage, BUCT630, from hospital sewage water targeting antibiotic-resistant E. faecium. Physiological characterization revealed that BUCT630 had a long adsorption time (50 min) and moderate burst size (130 PFU/cell), had relatively favourable stability in both acidic and alkaline environments, and withstand 50°C high temperature. Transmission electron microscopy (TEM) revealed that phage BUCT630 belongs to the unclassified Caudoviricetes through a phylogenetic tree based on a terminase large subunit and whole genome sequence. The host range was comparatively broad and can lyse 8 of 18 Enterococcus strains. Through BLASTn analysis, BUCT630 had 69% query coverage and 89% sequence identity with other phages in the database. The genomic analysis disclosed that phage BUCT630 is linear dsDNA with 41,942 bp having 35% GC content and comprises 61 open reading frames (ORF) free from antibiotic and virulence genes. Furthermore, BUCT630 in vitro could efficiently inhibit the E. faecium growth, and in vivo, it increased the survival rate to 90% in the Galerria mellonela model. Our findings revealed that BUCT630 is a promising therapeutic option for combating antibiotic resistant E. faecium infections.
Insights
A novel lytic phage, BUCT630, effectively targets antibiotic-resistant Enterococcus faecium. This phage demonstrates significant potential as a therapeutic alternative to antibiotics for treating resistant bacterial infections.
Area of Science:
- Microbiology
- Bacteriology
- Genomics
Background:
- Antibiotic-resistant Enterococcus faecium poses a significant global health threat.
- Conventional antibiotics are becoming less effective against resistant strains.
- Bacteriophages (phages) are emerging as a promising alternative therapy.
Purpose of the Study:
- To isolate and characterize a novel lytic phage targeting antibiotic-resistant E. faecium.
- To evaluate the therapeutic potential of the isolated phage BUCT630.
- To assess the safety and efficacy of phage BUCT630 in vitro and in vivo models.
Main Methods:
- Isolation and characterization of lytic phage BUCT630 from hospital sewage.
- Physiological stability testing (pH, temperature, adsorption, burst size).
- Transmission electron microscopy (TEM) and whole-genome sequencing for phylogenetic analysis.
- Host range determination and in vitro/in vivo efficacy testing (Galleria mellonela model).
Main Results:
- Phage BUCT630, a Caudoviricetes, exhibits favorable stability and a broad host range against E. faecium.
- Genomic analysis revealed a linear dsDNA genome (41,942 bp) devoid of antibiotic resistance or virulence genes.
- In vitro studies showed efficient inhibition of E. faecium growth.
- In vivo studies in Galleria mellonela demonstrated a 90% survival rate.
Conclusions:
- Phage BUCT630 is a robust lytic phage with a promising safety and efficacy profile.
- BUCT630 represents a viable therapeutic candidate for combating antibiotic-resistant E. faecium infections.
- Further research into phage therapy is warranted for addressing multidrug-resistant bacterial pathogens.
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