Characterization and therapeutic potential of two Kayvirus phages against methicillin-resistant S. aureus in a rat myositis model
European Journal of Clinical Microbiology and Infectious Diseases, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s10096-026-05604-3
- Dergi Adı: European Journal of Clinical Microbiology and Infectious Diseases
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, Environment Index, MEDLINE, Public Affairs Index, Academic Search Ultimate (EBSCO), Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest)
- Anahtar Kelimeler: Kayvirus phages, Methicillin-resistant S. aureus, Myositis model, Phage therapy
- Yıldız Teknik Üniversitesi Adresli: Evet
Özet
Purpose: Methicillin-resistant Staphylococcus aureus (MRSA) continues to compromise the efficacy of conventional antibiotics, highlighting the urgent need for alternative antimicrobial strategies. This study aimed to isolate, characterize, and evaluate the therapeutic potential of two strictly lytic bacteriophages, Staphylococcus phages EAS1 and EAS2, against MRSA, including their safety and efficacy in an in vivo myositis model. Methods: EAS1 and EAS2 were isolated from wastewater and characterized using transmission electron microscopy, whole-genome sequencing, and in vitro functional assays. Genomic and comparative analyses were performed to assess genome organization and safety-related features. Therapeutic efficacy and toxicity were evaluated in a rat model of MRSA-induced myositis, with assessment of inflammatory mediators and histopathological tissue damage. Results: Both phages exhibited broad and potent lytic activity against S. aureus, including MRSA strains, and demonstrated high physicochemical stability and biocompatibility. Both phages possessed large linear dsDNA genomes (∼138–140 kb) encoding over 240 CDSs without lysogeny, virulence, or antibiotic resistance genes and were classified within the Kayvirus genus based on comparative genomics. In vivo, phage treatment caused no detectable hepatic or renal toxicity. EAS2 treatment led to significant modulation of inflammatory mediators, including TNF-α, IL-10, NF-κB, and COX-2, and resulted in reduced histopathological tissue damage compared with untreated control and vancomycin-treated groups. Conclusion: These findings demonstrate the stability, safety, and therapeutic efficacy of bacteriophages EAS1 and EAS2, particularly EAS2, supporting phage therapy as a promising alternative approach for the treatment of MRSA infections.