Novel Enterococcus phage BUCT630: Isolation and genomic insights targeting drug-resistant Enterococcus faecium in vitro and in vivo

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.