# Phage-antibiotic synergistic effect for treating cutaneous wounds infections caused by MRSA and the assessment of wound healing biomarkers in a rabbit model

## TL;DR

This study explores using bacteriophages with antibiotics to treat MRSA-infected wounds in rabbits, showing improved healing and reduced inflammation.

## Contribution

This is the first in vivo study combining temperate phages with antibiotics to treat MRSA wounds, demonstrating phage-antibiotic synergy.

## Key findings

- Phage treatment alone achieved 87.89% wound healing, increasing to 93.63% with vancomycin.
- Phage-antibiotic combination elevated collagen and growth factors while reducing pro-inflammatory cytokines.
- Immunohistochemistry confirmed decreased IL-6 and TNF-α in wound inflammatory cells.

## Abstract

Antibiotic-resistant methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge in managing wound infections. Bacteriophage therapy has emerged as a promising alternative or adjunct to traditional antibiotics. This study evaluated the therapeutic potential of a temperate, uncharacterized phage preparation induced from the S. aureus reference strain ATCC 25,923 using mitomycin C (MitC) for topical treatment of superficial MRSA-infected wounds in a rabbit model, both alone and combined with vancomycin. Key wound healing markers (collagen 1, MMP1, PDGF, FGF2) and inflammatory cytokines (IL-1, IL-6, TNF-α) were assessed alongside immunohistochemical analysis of IL-6 and TNF-α expression. The induced lysogenic phage demonstrated lytic activity against MRSA, resulting in a wound healing rate of 87.89%, which increased to 93.63% with combined vancomycin treatment. Enhanced healing correlated with elevated collagen, PDGF, and FGF2 expression and significant downregulation of pro-inflammatory cytokines (p < 0.0001). Immunohistochemistry confirmed decreased IL-6 and TNF-α expression in wound inflammatory cells. These findings provide preliminary in vivo evidence supporting phage-antibiotic synergy for treating MRSA wounds. Although promising, the phage preparation remains uncharacterized, limiting reproducibility and translational readiness. Further research is needed to characterize active phage components, evaluate safety, and optimize therapeutic protocols before clinical application. This study pioneers the in vivo use of temperate phages combined with antibiotics for MRSA wound treatment, addressing antibiotic resistance issues by improving wound closure, promoting healing factor expression, and reducing inflammation. These results lay an important foundation for developing novel therapies against resistant bacterial infections.

The online version contains supplementary material available at 10.1038/s41598-025-34474-6.