Characterization of the Hemorrhagic Reaction Caused by Vibrio vulnificus Metalloprotease, a Member of the Thermolysin Family

Vibrio vulnificus is an opportunistic human pathogen causing wound infections and septicemia, characterized by hemorrhagic and edematous damage to the skin. This human pathogen secretes a metalloprotease (V. vulnificus protease [VVP]) as an important virulence determinant. When several bacterial metalloproteases including VVP were injected intradermally into dorsal skin, VVP showed the greatest hemorrhagic activity. The level of the in vivo hemorrhagic activity of the bacterial metalloproteases was significantly correlated with that of the in vitro proteolytic activity for the reconstituted basement membrane gel. Of two major basement membrane components (laminin and type IV collagen), only type IV collagen was easily digested by VVP. Additionally, the immunoglobulin G antibody against type IV collagen, but not against laminin, showed sufficient protection against the hemorrhagic reaction caused by VVP. Capillary vessels are known to be stabilized by binding of the basal surface of vascular endothelial cells to the basement membrane. Therefore, specific degradation of type IV collagen may cause destruction of the basement membrane, breakdown of capillary vessels, and leakage of blood components including erythrocytes.

创伤弧菌（Vibrio vulnificus）是一种机会致病性人类致病菌，可引发伤口感染与败血症，其特征为皮肤出现出血性与水肿性损伤。该人类致病菌会分泌金属蛋白酶（创伤弧菌蛋白酶[VVP]），这是其重要的毒力决定因子。当包括VVP在内的多种细菌金属蛋白酶被皮内注射至背部皮肤时，VVP展现出最强的出血活性。细菌金属蛋白酶的体内出血活性水平，与它们对重组基底膜凝胶的体外蛋白水解活性水平显著相关。在两种主要基底膜组分（层粘连蛋白与IV型胶原）中，仅IV型胶原可被VVP轻易降解。此外，针对IV型胶原而非层粘连蛋白的免疫球蛋白G抗体，能够充分抵御VVP引发的出血反应。已知毛细血管可通过血管内皮细胞基底表面与基底膜的结合来维持稳定。因此，IV型胶原的特异性降解可能会导致基底膜破坏、毛细血管破裂，以及包括红细胞在内的血液成分渗漏。