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Antimicrobial Agents and Chemotherapy, February 2007, p. 446-452, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.00635-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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

Ryohei Watanabe,1 Tetsuya Matsumoto,2* Go Sano,3 Yoshikazu Ishii,4 Kazuhiro Tateda,4 Yoshinobu Sumiyama,1 Jumpei Uchiyama,5 Shingo Sakurai,5 Shigenobu Matsuzaki,5 Shosuke Imai,5 and Keizo Yamaguchi4

Third Department of Surgery, Toho University School of Medicine,1 Department of Microbiology, Tokyo Medical University,2 Department of Respiratory Medicine, Toho University Omori Medical Center,3 Department of Microbiology and Infectious Diseases, Toho University School of Medicine,4 Department of Molecular Microbiology and Infections, Kochi Medical School, Tokyo, Japan5

Received 24 May 2006/ Returned for modification 23 June 2006/ Accepted 7 November 2006

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-{alpha}, interleukin-1ß [IL-1ß], 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.

* Corresponding author. Mailing address: Department of Microbiology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan. Phone: 81-3-3351-6141. Fax: 81-3-3351-6160. E-mail: tetsuya{at}tokyo-med.ac.jp.

{triangledown} Published ahead of print on 20 November 2006.

Antimicrobial Agents and Chemotherapy, February 2007, p. 446-452, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.00635-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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