Regulation of proteolytic activity of Vibrio vulnificus by iron-containing compounds

Previous studies have shown that the Vibrio vulnificus is able to use hemoglobin and the hemoglobin-haptoglobin complex to reverse iron limitation. In addition, we report here that free hemin, as well as hemin bound to albumin, will reverse iron-limited growth. While protease negative mutants were able to use hemin and hemoglobin, they were unable to compete as successfully for albumin-bound hemin. Using Luria broth with the iron chelator ethylenediamine-di(o-hydroxyphenylacetic acid) (EDDA), no changes in proteolytic activity were seen. In contrast, growth in a low iron defined medium resulted in a loss of proteolytic activity. This loss was reversed by the addition of hemin or hemoglobin but not by inorganic iron or globin alone. Since one portal of entry of this organism is pre-existing wounds, hemoglobin released during cell damage may be important in activating extracellular proteases leading to the massive cell damage seen with this vibrio.