Efficacy of Bacteriophage Therapy against Gut-Derived Sepsis Caused by Pseudomonas aeruginosa in Mice

Author:

Watanabe Ryohei1,Matsumoto Tetsuya2,Sano Go3,Ishii Yoshikazu4,Tateda Kazuhiro4,Sumiyama Yoshinobu1,Uchiyama Jumpei5,Sakurai Shingo5,Matsuzaki Shigenobu5,Imai Shosuke5,Yamaguchi Keizo4

Affiliation:

1. Third Department of Surgery, Toho University School of Medicine

2. Department of Microbiology, Tokyo Medical University

3. Department of Respiratory Medicine, Toho University Omori Medical Center

4. Department of Microbiology and Infectious Diseases, Toho University School of Medicine

5. Department of Molecular Microbiology and Infections, Kochi Medical School, Tokyo, Japan

Abstract

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 .

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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