Vibrio vulnificus vulnibactin, but not metalloprotease VvpE, is essentially required for iron-uptake from human holotransferrin

Abstract

The roles of metalloprotease (VvpE) and catechol-siderophore (vulnibactin) in the uptake of iron from human transferrins by Vibrio vulnificus have been determined using different experimental conditions and methods. Therefore, in this study, we attempted to elucidate the roles of VvpE and vulnibactin using the same methods and experimental conditions, in an in vitro and a human ex vivo system, and in accordance with the molecular version of Koch's postulates. Neither vvpE mutation nor in trans vvpE complementation affected vulnibactin production, iron-assimilation from human holotransferrin (HT), and bacterial growth in a HT-containing deferrated Heart-Infusion medium (HT-DF-HI) or a HT-containing cirrhotic ascites (HT-CA). In contrast, the mutation of fur gene encoding Fur, a repressor regulating expression of the vulnibactin-mediated iron-uptake system, derepressed vulnibactin production, and facilitated iron-assimilation from HT and bacterial growth in HT-DF-HI or HT-CA. The mutation of vis gene encoding isochorismate synthase required for vulnibactin synthesis abolished vulnibactin production, iron-assimilation from HT and bacterial growth in HT-DF-HI or HT-CA. These results demonstrate that vulnibactin is essentially required for iron-assimilation from transferrin, and that VvpE has no direct effect on facilitating vulnibactin-mediated iron-assimilation from transferrin in vitro or in a human ex vivo system. © 2006 Pharmaceutical Society of Japan.