Characterization and Therapeutic Potential of a Novel Bacteriophage Targeting Methicillin-Resistant Staphylococcus...

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of multidrug-resistant and biofilm-associated infections, particularly on indwelling medical devices, where conventional antibiotics often exhibit limited efficacy. In this study, we isolated and characterized a novel lytic bacteriophage, SA_SGEB_01, targeting MRSA from hospital wastewater in Bangladesh. Biological characterization demonstrated that SA_SGEB_01 possesses favorable therapeutic properties, including a short latent period (~45 min), a burst size of approximately 91 plaque-forming units per infected cell, and stability across a broad pH range (3-11) and temperatures up to 45°C. Host range analysis revealed lytic activity against MRSA and methicillin-resistant Staphylococcus saprophyticus. Whole-genome sequencing showed that SA_SGEB_01 contains a linear double-stranded DNA genome of 18,031 bp with no detectable lysogeny-associated, antibiotic resistance, or virulence genes, supporting its therapeutic suitability. Comparative genomic and phylogenetic analyses classified the phage within the genus Rosenblumvirus of the family Rountreeviridae. Phage-antibiotic checkerboard assays demonstrated strong synergistic activity between SA_SGEB_01 and ciprofloxacin, with fractional inhibitory concentration index values below 0.5. Importantly, SA_SGEB_01 significantly reduced biofilm biomass in both 24- and 48-h-old MRSA biofilms and achieved approximately a 2-log₁₀ reduction of viable cells in in vitro silicone catheter-associated biofilms, whereas vancomycin did not produce a statistically significant reduction under the same experimental conditions. To our knowledge, this is the first biologically and genomically characterized S. aureus phage from Bangladesh with demonstrated activity against MDR MRSA biofilms, highlighting its potential as a promising candidate for controlling device-associated MRSA infections.