Genomic and phenotype-based framework for rational design of phage cocktails against Escherichia coli isolates from urinary tract infections
- 1Universite de Sherbrooke
Abstract
Urinary tract infections (UTIs) are frequently caused by Escherichia coli and are increasingly associated with antimicrobial resistance, highlighting the need for alternative therapies. Although phage therapy is a promising approach, the rational selection of phages and phage cocktails remains challenging, particularly when detailed genomic information on the infecting strain is unavailable. In this study, we isolated 18 phages from environmental samples collected in Sherbrooke, Quebec, Canada. Genome sequencing identified 15 pure lytic phages representing diverse taxonomic groups and revealed prophage-derived contaminants in three isolates, underscoring the importance of genomic validation during phage discovery. Host range was determined using efficiency-of-plating (EOP) assays against UTI-associated E. coli isolates. Based on host-range overlap and cumulative EOP values, we developed a phenotype-based framework for phage cocktail design and classified combinations as redundant or complementary. Complementary cocktails composed of phages with distinct host ranges and high infection effectiveness consistently outperformed redundant combinations in time-kill assays, demonstrating that host-range diversity and lytic effectiveness are independent properties that should be considered separately during cocktail design. To evaluate cocktail performance under physiologically relevant conditions, the most effective combinations were tested in artificial urine. Both cocktails exhibited reduced activity compared with standard laboratory media, indicating that environmental conditions strongly influence phage-host interactions. Together, our results demonstrate that host-range overlap and cumulative infection effectiveness provide a practical framework for identifying effective phage combinations in the absence of detailed bacterial genomic information and may facilitate the rational development of phage therapies for UTIs.
Related
- Isolation, identification, and slow-growth phenotype characterization of a clinically derived Escherichia coli from urinary tract infection
- Whole-genome sequencing-based characterization of antimicrobial resistance determinants and phenotype–genotype concordance in uropathogenic Escherichia coli isolates from ICU patients in Saudi Arabia
- Receptor-guided phage cocktails constrain Acinetobacter baumannii resistance and improve therapy
- An Evidence-Tiered Developmental Framework for Congenital Vertebral Malformations: Spatiotemporal Thresholds in Genotype–Phenotype Interpretation
- Formulation, stability, and delivery of bacteriophage cocktails in veterinary medicine: a review of physicochemical constraints and therapeutic outcomes in production animals
BibTeX
@misc{silva2026genomic,
title = {{Genomic and phenotype-based framework for rational design of phage cocktails against Escherichia coli isolates from urinary tract infections}},
author = {P. Ugalde Silva and A. Champoux and A. Chenard and S. Tuytschaevers and E. Jolicoeur and N. Rivard and L.-C. Fortier},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.24.754182},
url = {https://www.biorxiv.org/content/10.64898/2026.09.24.754182v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Genomic and phenotype-based framework for rational design of phage cocktails against Escherichia coli isolates from urinary tract infections
AU - P. Ugalde Silva
AU - A. Champoux
AU - A. Chenard
AU - S. Tuytschaevers
AU - E. Jolicoeur
AU - N. Rivard
AU - L.-C. Fortier
PY - 2026
DA - 2026/09/24
PB - bioRxiv
DO - 10.64898/2026.09.24.754182
UR - https://www.biorxiv.org/content/10.64898/2026.09.24.754182v1
AB - Urinary tract infections (UTIs) are frequently caused by Escherichia coli and are increasingly associated with antimicrobial resistance, highlighting the need for alternative therapies. Although phage therapy is a promising approach, the rational selection of phages and phage cocktails remains challenging, particularly when detailed genomic information on the infecting strain is unavailable. In this study, we isolated 18 phages from environmental samples collected in Sherbrooke, Quebec, Canada. Genome sequencing identified 15 pure lytic phages representing diverse taxonomic groups and revealed prophage-derived contaminants in three isolates, underscoring the importance of genomic validation during phage discovery. Host range was determined using efficiency-of-plating (EOP) assays against UTI-associated E. coli isolates. Based on host-range overlap and cumulative EOP values, we developed a phenotype-based framework for phage cocktail design and classified combinations as redundant or complementary. Complementary cocktails composed of phages with distinct host ranges and high infection effectiveness consistently outperformed redundant combinations in time-kill assays, demonstrating that host-range diversity and lytic effectiveness are independent properties that should be considered separately during cocktail design. To evaluate cocktail performance under physiologically relevant conditions, the most effective combinations were tested in artificial urine. Both cocktails exhibited reduced activity compared with standard laboratory media, indicating that environmental conditions strongly influence phage-host interactions. Together, our results demonstrate that host-range overlap and cumulative infection effectiveness provide a practical framework for identifying effective phage combinations in the absence of detailed bacterial genomic information and may facilitate the rational development of phage therapies for UTIs.
ER -