MOUSE SKIN DAMAGE CAUSED BY A RECOMBINANT EXTRACELLULAR METALLOPROTEASE FROM VIBRIO-VULNIFICUS AND BY V-VULNIFICUS INFECTION

Vibrio vulnificus wound infection is characterized by an intense acute cellulitis which spreads along the subcutaneous tissue with severe ti ssue destruction. Toxins produced by the bacteria appear to be involve d in the pathogenesis of skin necrosis and to facilitate microbial dis semination in vivo. We report microscopic studies of mouse skin damage caused by a single intradermal injection of V. vulnificus or of an ex tracellular metalloprotease isolated from this organism. The gene enco ding this metalloprotease has been cloned and expressed in Escherichia coli. The crude metalloprotease extract obtained from the periplasmic fraction by osmotic shock was used in this study. Intradermal injecti on of this preparation resulted in marked edematous changes of the ski n, which extended throughout the dermis and subcutaneous tissues and i nto adjacent muscles. The collagen and elastic fibers degenerated and some muscle cells even appeared necrotic. Blood vessels became congest ed, with moderate perivascular neutrophil and mononuclear cell infiltr ation. There was no evidence of necrotic changes in the blood vessel i tself. These results show that the damage to the connective tissues ca used by V. vulnificus at least partly attributable to its protease. Th erefore, the protease seems to be an important virulence factor of thi s microbe.