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Updated: May 17, 2026
Establishing a Porcine Ex Vivo Cornea Model for Studying Drug Treatments against Bacterial Keratitis
Published on: May 12, 2020
Pseudomonas aeruginosa keratitis in mice: effects of topical bacteriophage KPP12 administration
Ken Fukuda1, Waka Ishida, Jumpei Uchiyama
1Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi, Japan. k.fukuda@kochi-u.ac.jp
Abstract:
The therapeutic effects of bacteriophage (phage) KPP12 in Pseudomonas aeruginosa keratitis were investigated in mice. Morphological analysis showed that phage KPP12 is a member of the family Myoviridae, morphotype A1, and DNA sequence analysis revealed that phage KPP12 is similar to PB1-like viruses. Analysis of the phage KPP12 genome did not identify any genes related to drug resistance, pathogenicity or lysogenicity, and so phage KPP12 may be a good candidate for therapeutic. KPP12 showed a broad host range for P. aeruginosa strains isolated from clinical ophthalmic infections. 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. 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.
Insights
Bacteriophage KPP12 eye-drops effectively treated Pseudomonas aeruginosa keratitis in mice. This therapy reduced inflammation and cleared bacteria, offering a potential alternative for antibiotic-resistant infections.
Area of Science:
- Ophthalmology
- Microbiology
- Virology
Background:
- Pseudomonas aeruginosa keratitis is a severe eye infection often resistant to antibiotics.
- Bacteriophages (phages) are viruses that infect bacteria and are being explored as therapeutic agents.
Purpose of the Study:
- To investigate the therapeutic efficacy of bacteriophage KPP12 against Pseudomonas aeruginosa keratitis in a mouse model.
- To assess the safety and effectiveness of phage KPP12 as an eye-drop treatment.
Main Methods:
- Morphological and genomic analysis of bacteriophage KPP12.
- Induction of keratitis in mice by P. aeruginosa inoculation.
- Treatment with single-dose KPP12 eye-drops and subsequent evaluation of disease outcome.
Main Results:
- Phage KPP12, a Myoviridae family member, demonstrated no genes for drug resistance, pathogenicity, or lysogenicity.
- KPP12 showed a broad host range against clinical P. aeruginosa strains.
- KPP12 eye-drops significantly improved keratitis, preserved corneal integrity, reduced neutrophil infiltration, and enhanced bacterial clearance.
Conclusions:
- Bacteriophage KPP12 is a safe and effective therapeutic candidate for P. aeruginosa keratitis.
- Phage therapy offers a promising alternative or adjunctive treatment for antibiotic-resistant bacterial keratitis.