Therapeutic Effects of Topical Bacteriophage KPP12 Administration on Pseudomonas aeruginosa Keratitis in Mice

Abstract

Purpose: : Pseudomonas aeruginosa (P. aeruginosa) is an important cause of destructive ocular infection, especially in contact lens wearers. Bacteriophages are viruses that are omnipresent in the environment. Bacteriophages infect, lyse, and kill bacteria without damage to mammalian cells. The aim of the present study was to investigate the therapeutic effects of single-dose administration of P. aeruginosa-specific bacteriophage eye-drops on P. aeruginosa keratitis in mice.

Methods: : Bacteriophage KPP12 was isolated from river water using a P. aeruginosa strain as the host. The mouse model of P. aeruginosa keratitis is induced by the application of P. aeruginosa to the scarified corneal surface in C57BL/6 mice. Thirty minutes after infection, bacteriophage in 5 μl or vehicle was applied to the corneal surface. The eyes were examined at 1, 3, and 5 days post-infection (p.i.) to grade disease severity. The number of viable bacteria and infiltrated neutrophils in the cornea were determined on day 5 p.i.

Results: : Inoculation of the scarified cornea with P. aeruginosa caused severe keratitis and eventual corneal perforation. Subsequent single-dose administration of KPP12 eye-drops significantly improved disease outcome, and preserved the structural integrity and transparency of the infected cornea. KPP12 treatment resulted in the suppression of neutrophil infiltration and greatly enhanced bacterial clearance in the infected cornea.

Conclusions: : These results indicate that bacteriophage eye-drops may be a novel adjunctive or alternative therapeutic agent for the treatment of infectious keratitis secondary to antibiotic-resistant bacteria.

Keywords: bacterial disease • cornea: basic science • pseudomonas