This Article Full Text Full Text (PDF) Other Versions of this Article: AAC.00635-06v1 51/2/446    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Watanabe, R. Articles by Yamaguchi, K. Search for Related Content PubMed PubMed Citation Articles by Watanabe, R. Articles by Yamaguchi, K.

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

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-, 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.

Published ahead of print on 20 November 2006.

This article has been cited by other articles:

• Uchiyama, J., Rashel, M., Takemura, I., Wakiguchi, H., Matsuzaki, S. (2008). In Silico and In Vivo Evaluation of Bacteriophage {phi}EF24C, a Candidate for Treatment of Enterococcus faecalis Infections. Appl. Environ. Microbiol. 74: 4149-4163 [Abstract] [Full Text]  
• Williams, S. R., Gebhart, D., Martin, D. W., Scholl, D. (2008). Retargeting R-Type Pyocins To Generate Novel Bactericidal Protein Complexes. Appl. Environ. Microbiol. 74: 3868-3876 [Abstract] [Full Text]  
• Scholl, D., Martin, D. W. Jr. (2008). Antibacterial Efficacy of R-Type Pyocins towards Pseudomonas aeruginosa in a Murine Peritonitis Model. Antimicrob. Agents Chemother. 52: 1647-1652 [Abstract] [Full Text]