Biocontrol of methicillin-resistant Staphylococcus aureus using a virulent bacteriophage derived from a temperate one

Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to global public health due to its resistance to specific antibiotics. Bacteriophages particularly the lytic ones are promoted as a potential powerful-tool to combat infections caused by drug resistant bacteria; while several disadvantages limited the application of the temperate ones. In this study, we isolated 14 phages against MRSA strains, and found three ones showed the capacity of killing most of the target MRSA strains. However, whole genome sequencing and generation of lysogens indicated that these three bacteriophage candidates were temperate ones. Therefore, we mutated one (4PHSA25) of them to a virulent bacteriophage (4PHCISA25). Phenotypical characterization assays revealed that 4PHCISA25 had similar lytic spectrum, temperature, pH, and UV sensitivities to 4PHSA25. However, 4PHCISA25 displayed increased lytic activities and decreased bacteriophage insensitive mutant frequency. Biofilm removing assays showed that 4PHCISA25 exhibited a better capacity than 4PHSA25 on eliminating biofilms formed by MRSA strains. Mouse experiments demonstrated that injection of 4PHCISA25 was safe to the mice and treatment with it (10⁹ PFU per mouse) inhibited the development of abscess induced by MRSA within 24 h and promoted the recovery from the clinical signs. Taken together, this study highlights the use of phages combating MRSA.