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Infection and Immunity, November 2002, p. 6251-6262, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.6251-6262.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Phage Therapy of Local and Systemic Disease Caused by Vibrio vulnificus in Iron-Dextran-Treated Mice

Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida 32610,¹ Gulf Coast Seafood Laboratory, U.S. Food and Drug Administration, Dauphin Island, Alabama 36528²

Received 28 January 2002/ Returned for modification 29 March 2002/ Accepted 29 July 2002

Vibrio vulnificus is a gram-negative bacterium that contaminates filter-feeding shellfish such as oysters. After ingestion of contaminated oysters, predisposed people may experience highly lethal septicemia. Contamination of wounds with the bacteria can result in devastating necrotizing fasciitis, which can progress to septicemia. The extremely rapid progression of these diseases can render antibiotic treatment ineffective, and death is a frequent outcome. In this study, we examined the potential use of bacteriophages as therapeutic agents against V. vulnificus in an iron-dextran-treated mouse model of V. vulnificus infection. Mice were injected subcutaneously with 10 times the lethal dose of V. vulnificus and injected intravenously, either simultaneously or at various times after infection, with phages. Treatment of mice with phages could prevent death; systemic disease, as measured by CFU per gram of liver and body temperature; and local disease, as measured by CFU per gram of lesion material and histopathologic analysis. Two different phages were effective against three different V. vulnificus strains with various degrees of virulence, while a third phage that required the presence of seawater to lyse bacteria in vitro was ineffective at treating mice. Optimum protection required that the phages be administered within 3 h of bacterial inoculation at doses as high as 10⁸ PFU. One of the protective phages had a half-life in blood of over 2 h. These results demonstrate that bacteriophages have therapeutic potential for both localized and systemic infections caused by V. vulnificus in animals. This model should be useful in answering basic questions regarding phage therapy.

Editor: J. T. Barbieri

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