Open AccessEfficacy of Bacteriophage Therapy against Gut-Derived Sepsis Caused by Pseudomonas aeruginosa in Mice
Author(s) -
Ryohei Watanabe,
Tetsuya Matsumoto,
Go Sano,
Yoshikazu Ishii,
Kazuhiro Tateda,
Yoshinobu Sumiyama,
Jumpei Uchiyama,
Shingo Sakurai,
Shigenobu Matsuzaki,
Shosuke Imai,
Keizo Yamaguchi
Publication year - 2007
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00635-06
Subject(s) - bacteriophage , pseudomonas aeruginosa , sepsis , lytic cycle , spleen , phage therapy , microbiology and biotechnology , gastrointestinal tract , biology , tumor necrosis factor alpha , bacteremia , saline , immunology , bacteria , antibiotics , escherichia coli , virus , endocrinology , biochemistry , genetics , gene
We evaluated the efficacy of bacteriophage (phage) therapy by using a murine model of gut-derived sepsis caused byPseudomonas aeruginosa that closely resembles the clinical pathophysiology of septicemia in humans. Oral administration of a newly isolated lytic phage strain (KPP10) significantly protected mice against mortality (survival rates, 66.7% for the phage-treated group versus 0% for the saline-treated control group;P < 0.01). Mice treated with phage also had lower numbers of viableP. aeruginosa cells in their blood, liver, and spleen. The levels of inflammatory cytokines (tumor necrosis factor alpha TNF-α, interleukin-1β [IL-1β], and IL-6) in blood and liver were significantly lower in phage-treated mice than in phage-untreated mice. The number of viableP. aeruginosa cells in fecal matter in the gastrointestinal tract was significantly lower in phage-treated mice than in the saline-treated control mice. We also studied the efficacy of phage treatment for intraperitoneal infection caused byP. aeruginosa and found that phage treatment significantly improved the survival of mice, but only under limited experimental conditions. In conclusion, our findings suggest that oral administration of phage may be effective against gut-derived sepsis caused byP. aeruginosa .