Work

Characterization of novel phage Henuyfy11N: a potential therapeutic agent against extended-spectrum β-lactamase (ESBL)-producing Escherichia coli

Year: 2026

Type: article

Abstract: ABSTRACT Escherichia coli is a major cause of hospital-acquired infections in China, including urinary tract, bloodstream, and intestinal infections. Given the rising prevalence of antibiotic-resistant E. coli , phages are increasingly regarded as promising alternatives to conventional antibiotics. Henuyfy11N was isolated using the double-layer agar method and characterized via transmission electron microscopy in this study. Biological assays included stability under varying pH and temperature, UV sensitivity, host range, optimal multiplicity of infection, adsorption rate, and one-step growth curve. In vitro lytic activity against extended-spectrum β-lactamase (ESBL)-producing E. coli and biofilm eradication capacity was assessed. Whole-genome sequencing enabled phylogenetic, synteny (the analysis of conserved blocks of genetic sequence between different genomes), and functional annotation analyses. In vivo , the therapeutic efficacy was evaluated in a mouse infection model. Phage Henuyfy11N has not yet been classified. It demonstrated high lytic activity, a short latent period, and a burst size of 57.1 PFU/cell. The phage remained stable across a broad pH range (3–11) and temperatures up to 70℃. Its circular double-stranded DNA genome (41,103 bp, G + C% 50.88) contains 54 open reading frames, with no tRNA, virulence, or antibiotic resistance genes. Genomic and phylogenetic analyses revealed close relatedness to phage BUCT789. Henuyfy11N effectively lysed ESBL-producing E. coli , disrupted biofilms, and significantly improved survival in the mouse infection model. Henuyfy11N shows high host specificity, efficient lytic activity, rapid replication, and a safe genomic profile, demonstrating some potential as a therapeutic agent against ESBL-producing E. coli infections. IMPORTANCE The widespread use of antibiotics has led to increasing antibiotic resistance, which is a growing global health concern. Therefore, the development of novel antimicrobial therapy that can cure drug-resistant bacteria-induced infections is imperative. Phages are of increasing interest as natural enemies of bacteria, with clear advantages in antibacterial applications. In this study, by using extended-spectrum β-lactamase (ESBL)-producing Escherichia coli 2025011N as a host, we successfully isolated and purified Escherichia phage Henuyfy11N and conducted a series of experiments to verify its genomic character and biological character. Our findings revealed that the phage exhibited excellent tolerance to a broad spectrum of pH and wide temperature range. Phage Henuyfy11N was effective in disrupting mature biofilm, and no genes for virulence, lysogenic, integrase, or AMRs were found in the genome. Besides, Henuyfy11N showed promising antibacterial effects in vivo and in vitro , indicating potential as a therapeutic agent against ESBL-producing E. coli infections.

Source: Microbiology Spectrum

DOI: 10.1128/spectrum.03253-25

Authors: Xinwei Zhang, Jiaqi He, Dongliang Qiao, Qiming Li, Zhigang Liu, Li Wang

Institution: First Affiliated Hospital of Henan University

Language: English

Topic: Bacteriophages and microbial interactions

Subfield: Ecology

Field: Environmental Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,500