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Infection and Immunity, October 1998, p. 4851-4855, Vol. 66, No. 10
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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

Shin-ichi Miyoshi,1,* Hiromi Nakazawa,1 Koji Kawata,1 Ken-ichi Tomochika,1 Kazuo Tobe,2 and Sumio Shinoda1

Faculty of Pharmaceutical Sciences1 and Health and Medical Center,2 Okayama University, Tsushima-Naka, Okayama 700-8530, Japan

Received 16 December 1997/Returned for modification 10 March 1998/Accepted 2 July 1998

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.

* Corresponding author. Mailing address: Faculty of Pharmaceutical Sciences, Okayama University, Tsushima-Naka, Okayama 700-8530, Japan. Phone: 81-86-251-7968. Fax: 81-86-251-7926. E-mail: miyoshi{at}pheasant.pharm.okayama-u.ac.jp.

Infection and Immunity, October 1998, p. 4851-4855, Vol. 66, No. 10
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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