The treatment of endophthalmitis is challenging due to the emergence of MDR bacteria. We evaluated the therapeutic potential of Ply187AN-KSH3b, a chimeric phage endolysin derived from the Ply187 prophage in a mouse model of Staphylococcus aureus endophthalmitis. The endolysin was injected intravitreally in C57BL/6 mouse eyes at 6 h and 12 h post S. aureus infection. The disease progression was monitored by ophthalmoscopic, electroretinography, histological, cell death and microbiological parameters. Expression of cytokines/chemokines and cellular infiltration was assessed. Intravitreal injection of chimeric Ply187AN-KSH3b (both at 6 and 12 h post infection) significantly improved the outcome of staphylococcal endophthalmitis, preserved retinal structural integrity, and maintained visual function. Phage lysin treatment significantly reduced the bacterial burden and the levels of inflammatory cytokines and neutrophil infiltration in the eyes. This is the first study demonstrating the therapeutic use of phage-based antimicrobials in ocular infections
