Diverse lytic bacteriophages from India reveal genomic signatures and therapeutic potential against MDR Escherichia coli

Background The rise of antimicrobial resistance (AMR) in Escherichia coli , particularly among animal-derived isolates, poses a major threat to public and veterinary health. With conventional antibiotics increasingly ineffective against multidrug-resistant (MDR) strains, alternative solutions are urgently needed. Lytic bacteriophages, known for their host specificity and potent antibacterial activity, offer a promising therapeutic option. However, limited genomic data on phages from diverse ecological contexts hinders comprehensive understanding of their diversity and functional potential. Methods This study aimed to isolate, characterize, and assess the therapeutic potential of lytic bacteriophages targeting MDR E. coli isolated from livestock. Phages were enriched from sewage samples using an MDR E. coli host. Plaque morphology was assessed for lytic characteristics. Thermal and pH stability were assessed under controlled incubation conditions. Host range was determined against 20 MDR E. coli strains from cattle, buffalo, and goat. Whole genome sequencing and annotation were performed to determine genetic features, taxonomic classification, safety, and phylogenetic relationships. Results Three lytic phages BASU E2, BASU E7, and BASU E10 were successfully isolated, producing clear plaques indicative of strong lytic activity. All phages remained viable at 37°C and 42°C and within pH 6–9, but were inactivated at 80°C and at highly acidic or alkaline conditions. BASU E7 exhibited the broadest host range, lysing 75% of the tested strains. Genome analysis revealed double-stranded DNA genomes of approximately 157 kb (BASU E2), 50 kb (BASU E7), and 48 kb (BASU E10), with G + C content ranging from 44.62–45.47%. Taxonomically, BASU E2 was classified under Ackermannviridae , while BASU E7 and BASU E10 belonged to Siphoviridae , all within Caudovirales . All phages were predicted to be strictly lytic, lacking genes associated with lysogeny, antibiotic resistance, or virulence. Phylogenetic analysis showed distinct cluster of BASU E2, suggesting divergent evolutionary origin from BASU E7 and BASU E10. Conclusion This study presents the isolation of genetically safe, environmentally stable, and broadly active lytic phages effective against MDR E. coli of animal origin. These findings highlight the potential of these phages for use in veterinary phage therapy. However, further in vivo validation and the development of phage cocktails are necessary to advance their clinical application.