Affiliation:
1. Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, P.O. Box 100266, Gainesville, Florida 32610-0266
Abstract
ABSTRACT
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-Tn
5
Km2
phoA
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 Δ
fadR
mutation was complemented in
trans
with the wild-type gene. Further characterization of the Δ
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 Δ
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.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
25 articles.
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