Bacteriophage-derived ectolysin: a promising antimicrobial against fluoroquinolone-resistant MRSA.

BACKGROUND: Microbial keratitis remains one of the leading causes of blindness globally. With the rising threat of antimicrobial resistance, there is an urgent need for the development of novel antimicrobial agents with innovative mechanisms of action. MATERIAL AND METHODS: Antibacterial properties of P128, a peptidoglycan degrading enzyme derived from bacteriophage K, was determined against multi-drug resistant Staphylococcus aureus clinical strains. P128 was tested for its ocular safety in a rabbit corneal wound healing model. The antibacterial efficacy of P128 was investigated in in vivo rabbit and mouse infectious keratitis models. RESULTS: P128 demonstrated potent antibacterial activity against multidrug resistant S. aureus strains collected from patients with infectious keratitis, with minimum inhibitory concentrations ranging from 0.5 µg/mL to 16 µg/mL. Topical instillation of P128 to an injured cornea did not interfere with the re-epithelialisation rates nor cause any adverse effects. In a rabbit S. aureus keratitis model, P128 showed similar therapeutic efficacy to standard of care antibiotic, gatifloxacin. In a mouse model of fluoroquinolone-resistant methicillin-resistant S. aureus (MRSA) keratitis, P128 decreased the bacterial bioburden as well as corneal oedema. P128 displayed potent synergism with membrane active antimicrobial peptides, and their combination eradicated the preformed 96 hours biofilms. CONCLUSION: These results demonstrate the therapeutic potential of P128 for the management of drug-resistant MRSA keratitis and its combination with antimicrobial peptides may expand the antimicrobial armamentarium against biofilm-associated infections.