Dosing and delivery of bacteriophage therapy in a murine wound infection model

Lytic bacteriophages, viruses that lyse (kill) bacteria, hold great promise for treating infections, including wound infections caused by antimicrobial-resistant Pseudomonas aeruginosa. However, dosing and delivery strategies for phage therapy remain underdeveloped. In a mouse wound infection model specifically designed to evaluate the treatment of established infections—a critical gap in existing preclinical models—we investigated the impact of administration route, dose, and frequency on phage therapy efficacy. In this model, topical, but not systemic, delivery reduced wound bacterial burden. In vitro and in vivo data revealed rapid emergence of phage resistance and suggested potential benefit of using high and repeated doses. Building on these insights, we developed HydroPhage, a phage-containing hyaluronan-based hydrogel formed with dynamic covalent crosslinks that delivers high-titer phages over one week. Here, we show that sustained hydrogel-based delivery is a practical and effective approach for topical phage application. Here, the authors develop a mouse model of wound infection to evaluate the efficacy of phage therapy for established infections and generate “HydroPhage”, a phage-containing hydrogel, as a means for sustained delivery and topical phage application.

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Publication Details

Journal
Nature Communications
Published
2026-09-19
DOI
https://doi.org/10.1038/s41467-026-77992-1
Primary Topic
Bacteriophages and microbial interactions
Type
article
Field-Weighted Citation Impact
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article

Dosing and delivery of bacteriophage therapy in a murine wound infection model

Lucy J. Zhang, Francis G. Blankenberg, Ovijit Chaudhuri, Derek F. Amanatullah et al.
Nature Communications
Bacteriophages and microbial interactions
article

Dosing and delivery of bacteriophage therapy in a murine wound infection model

Lucy J. Zhang, Francis G. Blankenberg, Ovijit Chaudhuri, Derek F. Amanatullah, Nana Ansuah Peterson, Tejas Dharmaraj, Paul L. Bollyky, Tony H. Chang, Hunter A. Martinez, Julie D. Pourtois, Maryam Hajfathalian, Robert Manasherob, Aviv Hargil, Qingquan Chen, Cas de Leeuw, Arne Echterhof, Whitney Stannard, Zhiwei Li, Yung‐Hao Lin, Maya Abhyankar
article en

Abstract

Lytic bacteriophages, viruses that lyse (kill) bacteria, hold great promise for treating infections, including wound infections caused by antimicrobial-resistant Pseudomonas aeruginosa. However, dosing and delivery strategies for phage therapy remain underdeveloped. In a mouse wound infection model specifically designed to evaluate the treatment of established infections—a critical gap in existing preclinical models—we investigated the impact of administration route, dose, and frequency on phage therapy efficacy. In this model, topical, but not systemic, delivery reduced wound bacterial burden. In vitro and in vivo data revealed rapid emergence of phage resistance and suggested potential benefit of using high and repeated doses. Building on these insights, we developed HydroPhage, a phage-containing hyaluronan-based hydrogel formed with dynamic covalent crosslinks that delivers high-titer phages over one week. Here, we show that sustained hydrogel-based delivery is a practical and effective approach for topical phage application. Here, the authors develop a mouse model of wound infection to evaluate the efficacy of phage therapy for established infections and generate “HydroPhage”, a phage-containing hydrogel, as a means for sustained delivery and topical phage application.

Nature Communications
New Jersey Institute of Technology (US), Lucile Packard Children's Hospital (US), Radboud University Nijmegen (NL), Radboud University Medical Center (NL), University Hospital Münster (DE), Stanford Health Care (US), Radboud Institute for Molecular Life Sciences (NL), Stanford University (US)
Good health and well-being
Openalex Percentile: Top 11%
Bacteriophages and microbial interactions
DOIOpen Access PDFOpenAlex
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