Pseudomonas aeruginosa keratitis in mice: effects of topical bacteriophage KPP12 administration

• Published in: PloS one Vol. 7; no. 10; p. e47742
• Main Authors: Fukuda, Ken, Ishida, Waka, Uchiyama, Jumpei, Rashel, Mohammad, Kato, Shin-ichiro, Morita, Tamae, Muraoka, Asako, Sumi, Tamaki, Matsuzaki, Shigenobu, Daibata, Masanori, Fukushima, Atsuki
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.10.2012; Public Library of Science (PLoS)
• Subjects: Administration, Topical; Animals; Antibiotic resistance; Antibiotics; Bacteria; Bacterial infections; Bacterial Load; Bacteriophages; Bacteriophages - physiology; Bacteriophages - ultrastructure; Biology; Care and treatment; Chemical compounds; Cornea; Cornea - microbiology; Cornea - pathology; Deoxyribonucleic acid; Disease Progression; DNA; Drug resistance; Enzymes; Eye; Eye Infections, Bacterial - microbiology; Eye Infections, Bacterial - pathology; Eye Infections, Bacterial - therapy; Female; Genomes; Host range; Infiltration; Inoculation; Keratitis; Keratitis - microbiology; Keratitis - pathology; Keratitis - therapy; Laboratory animals; Medical schools; Medicine; Mice; Mice, Inbred C57BL; Neutrophil Infiltration; Nucleotide sequence; Pathogenicity; Pathogens; Perforation; Phages; Pharmacology; Pseudomonas aeruginosa; Pseudomonas aeruginosa - physiology; Pseudomonas aeruginosa infections; Pseudomonas Infections - microbiology; Pseudomonas Infections - pathology; Pseudomonas Infections - therapy; Science; Staphylococcus aureus; Staphylococcus infections; Streptococcus infections; Structural integrity; Studies; Transfer RNA; Transparency; Viruses; Eastern Europe; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0047742

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.