A new Kayvirus vB_SauM-MUHD-1 combats Methicillin-resistant Staphylococcus aureus wound infections

Methicillin-resistant Staphylococcus aureus (MRSA), a leading cause of chronic and post-surgical wound infections, is a hard-to-treat pathogen. In this study, we isolated and characterized a lytic MRSA bacteriophage, vB_SauM-MUHD-1, and evaluated its therapeutic potential in a murine wound infection model. Among 107 clinical wound samples, MRSA was reported in 48.6% of cases. Phage vB_SauM-MUHD-1, isolated from sewage, demonstrated lytic activity against 70.6% of the tested MRSA isolates. The phage exhibited efficient replication kinetics and remained stable under physiologically relevant conditions. Whole-genome sequencing identified a ~ 134 kb dsDNA genome (~ 30.45% GC) lacking detectable lysogeny-associated, virulence, or antimicrobial-resistance genes. In a BALB/c excisional wound model infected with MRSA, topical phage treatment significantly reduced bacterial burden, accelerated wound closure, and improved clinical severity scores compared to untreated controls, performing comparably to phage-linezolid combination therapy and outperforming linezolid monotherapy in bacterial clearance. These findings support that our phage vB_SauM-MUHD-1 has potential for treating MRSA-infected wounds and should be further investigated for efficacy in more challenging chronic or biofilm-rich wound environments. KEY POINTS: • This study provides a newly kayvirus, strictly lytic anti-MRSA phage vB_SauM-MUHD-1. • Phage exhibited favorable replication kinetics, physical stability and genomic safety. • Topical phage therapy reduced bacterial burden and accelerated wound healing.