# Receptor identification and in vivo efficacy of a lytic phage vB_EcoStr-FJ63A against colistin-resistant Escherichia coli

## TL;DR

This study identifies the host receptors of a phage effective against colistin-resistant E. coli and shows it reduces bacterial loads in mice.

## Contribution

The study identifies LPS and OmpC as receptors for phage vB_EcoStr-FJ63A and demonstrates its in vivo efficacy against drug-resistant E. coli.

## Key findings

- LPS is confirmed as a necessary receptor for phage vB_EcoStr-FJ63A adsorption.
- Phage vB_EcoStr-FJ63A reduces bacterial loads in blood and improves survival in infected mice.
- Phage remains detectable in mice blood for over 24 hours after administration.

## Abstract

Bacteriophages (phages), as natural predators of bacteria, represent promising alternatives to antibiotics. However, challenges such as narrow host range and insufficient pharmacokinetic and pharmacodynamic (PK/PD) studies restrict phage therapy. In previous work, we isolated Escherichia phage vB_EcoStr-FJ63A, which exhibits a lytic activity against colistin-resistant Escherichia coli and obvious antibacterial activity in vitro. To elucidate its infection mechanism and evaluate its therapeutic potential, this study focused on identifying its host receptors and assessing its in vivo efficacy. By screening resistant mutants and analyzing the function of mutant sites, we hypothesized that outer membrane proteins (OMPs), lipopolysaccharide (LPS), or extracellular polysaccharides likely serve as receptor candidates for phage vB_EcoStr-FJ63A. The role of LPS as the receptor was supported by competitive binding and receptor removal assays, which demonstrated its necessity for phage adsorption. Bioinformatics analysis results provide evidences for long tail fiber adhesin of phage vB_EcoStr-FJ63A reversibly binds to OmpC, while its short tail fibers irreversibly anchor to LPS. Subsequent PK experiment in healthy mice revealed that a single intraperitoneal injection of phage vB_EcoStr-FJ63A (5 × 108 PFU/mL or 5 × 106 PFU/mL) achieved peak blood titers at 2 h post-administration, with phage remaining detectable for over 24 h (n = 6 per group at each time point). In bacteremic mice infected with colistin-resistant E. coli, both phage doses significantly reduced bacterial loads in the blood within 8 h (n = 3 per group at each time point) and improved survival rates (n = 6 per group) compared with the untreated control group. Collectively, our results provide evidence for the molecular basis of phage–host interactions for vB_EcoStr-FJ63A and provides data to advance phage therapy against antimicrobial resistant E. coli.

The online version contains supplementary material available at 10.1186/s13567-025-01687-6.