Efficacy of bacteriophage therapy against gut-derived sepsis caused by Pseudomonas aeruginosa in mice

Ryohei Watanabe, Tetsuya Matsumoto, Go Sano, Yoshikazu Ishii, Kazuhiro Tateda, Yoshinobu Sumiyama, Jumpei Uchiyama, Shingo Sakurai, Shigenobu Matsuzaki, Shosuke Imai, Keizo Yamaguchi

Research output: Contribution to journalArticlepeer-review

155 Citations (Scopus)

Abstract

We evaluated the efficacy of bacteriophage (phage) therapy by using a murine model of gut-derived sepsis caused by Pseudomonas 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 viable P. 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 viable P. 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 by P. 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 by P. aeruginosa.

Original languageEnglish
Pages (from-to)446-452
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume51
Issue number2
DOIs
Publication statusPublished - Feb 2007
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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