Isolation of a transferrin-iron utilization mutant of Vibrio vulnificus by streptonigrin enrichment

Vibrio vulnificus infections are associated with septicemia and severe wound infections in patients with liver disease, immunocompromised states and iron overload. Mortality rate in septicemia cases approach 50%. V. vulnificus is highly dependent upon available iron sources for its pathogenicity. Prior studies have shown that V. vulnificus exhibits virulence in serum with 100% iron saturated transferring, but lacks virulence in serum with 30% saturated transferring. V. vulnificus strains have been found that lack a phenolate sideropore. These strains are unable to utilize transferring as an iron source and have shown avirulence in mice studies. These findings indicate a significant virulence factor of V. vulnificus is the utilization of transferring as a sole iron source. Therefore, iron overload, with resulting transferring saturation, is the most significant predisposing factor to high mortality in V. vulnificus infections. The specific aim of this project was to product a transferring-specific iron utilization mutant and study its related influence on virulence. TnphoA mutagenesis, in conjunction with streptonigrin enrichment for specific iron uptake mutations, successfully produced one transferring-iron uptake mutant. Further analysis showed that the organism was unable to produce catechol (phenolate) siderophones. This project is intended to increase our overall understanding of Vibrio vulnificus and its iron dependence and pathogenesis.