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Journal of Bacteriology, December 2008, p. 7633-7644, Vol. 190, No. 23
0021-9193/08/$08.00+0     doi:10.1128/JB.01016-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Regulation of Fatty Acid Metabolism by FadR Is Essential for Vibrio vulnificus To Cause Infection of Mice{triangledown}

Roslyn N. Brown and Paul A. Gulig*

Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, P.O. Box 100266, Gainesville, Florida 32610-0266

Received 23 July 2008/ Accepted 23 September 2008

The opportunistic bacterial pathogen Vibrio vulnificus causes severe wound infection and fatal septicemia. We used alkaline phosphatase insertion mutagenesis in a clinical isolate of V. vulnificus to find genes necessary for virulence, and we identified fadR, which encodes a regulator of fatty acid metabolism. The fadR::mini-Tn5Km2phoA mutant was highly attenuated in a subcutaneously inoculated iron dextran-treated mouse model of V. vulnificus disease, was hypersensitive to the fatty acid synthase inhibitor cerulenin, showed aberrant expression of fatty acid biosynthetic (fab) genes and fatty acid oxidative (fad) genes, produced smaller colonies on agar media, and grew slower in rich broth than did the wild-type parent. Deletion of fadR essentially recapitulated the phenotypes of the insertion mutant, and the {Delta}fadR mutation was complemented in trans with the wild-type gene. Further characterization of the {Delta}fadR mutant showed that it was not generally hypersensitive to envelope stresses but had decreased motility and showed an altered membrane lipid profile compared to that of the wild type. Supplementation of broth with the unsaturated fatty acid oleate restored wild-type growth in vitro, and infection with oleate in the inoculum increased the ability of the {Delta}fadR mutant to infect mice. We conclude that fadR and regulation of fatty acid metabolism are essential for V. vulnificus to be able to cause disease in mammalian hosts.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, P.O. Box 100266, Gainesville, FL 32610-0266. Phone: (352) 392-0050. Fax: (352) 392-3133. E-mail: gulig{at}ufl.edu

{triangledown} Published ahead of print on 3 October 2008.

Journal of Bacteriology, December 2008, p. 7633-7644, Vol. 190, No. 23
0021-9193/08/$08.00+0     doi:10.1128/JB.01016-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Brown, R. N., Gulig, P. A. (2009). Roles of RseB, {sigma}E, and DegP in Virulence and Phase Variation of Colony Morphotype of Vibrio vulnificus. Infect. Immun. 77: 3768-3781 [Abstract] [Full Text]  
  • Gulig, P. A., Tucker, M. S., Thiaville, P. C., Joseph, J. L., Brown, R. N. (2009). USER Friendly Cloning Coupled with Chitin-Based Natural Transformation Enables Rapid Mutagenesis of Vibrio vulnificus. Appl. Environ. Microbiol. 75: 4936-4949 [Abstract] [Full Text]  


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