Detachable dissolving microneedles loaded with Silviavirus phage Pelagios enhance antibacterial efficacy against methicillin resistant Staphylococcus aureus in ex vivo porcine skin.
Methicillin-resistant Staphylococcus aureus (MRSA) wound infections remain a major clinical challenge due to antibiotic resistance and biofilm persistence. Although phage therapy has re-emerged as a promising alternative, its efficacy is limited by poor stratum corneum penetration following conventional topical application. Here, we isolated and characterized a lytic MRSA phage, Pelagios, and evaluated its transdermal delivery using detachable dissolvable microneedles (DDMNs). Genomic analyses classified Pelagios within the genus Silviavirus of the family Herelleviridae and indicated that it may represent a novel species. The phage displayed rapid adsorption (∼15 min), a short latent period (∼20 min), a burst size of ∼102 PFU/cell, and stability across physiologically relevant temperature (4 °C -45 °C) and pH conditions (pH 4-10). Whole-genome sequencing confirmed the absence of toxin genes, virulence factors, antimicrobial resistance determinants, and lysogeny-associated genes, supporting its genomic safety. Pelagios exhibited broad lytic activity against multiple clinical MRSA isolates and significantly reduced planktonic bacterial populations both in vitro and in ex vivo porcine skin models in a dose-independent manner. It also effectively inhibited MRSA biofilm formation, although eradication of established biofilms was limited. Phage-loaded DDMNs fabricated from hyaluronic acid and gelatin achieved efficient skin penetration, rapid dissolution, complete needle detachment, and markedly improved phage stability at 4 °C. In ex vivo infection models, DDMN-mediated delivery significantly enhanced antibacterial and biofilm-eradicating efficacy compared with free phage suspension. These findings demonstrate that Pelagios delivered via DDMNs constitutes a safe and effective strategy for treating MRSA-associated wound and biofilm infections.