Vibrio vulnificus, an opportunistic human pathogen causing wound infection and septicemia, pro-duces a metalloprotease (VVP) which is suspected to be a virulent determinant. The interactions of VVP, as well as its derivative (PEG1-VVP) modified with polyethylene glycol, with a variety of human plasma pro-teins were investigated. We found that native VVP and its derivative were able to act directly on many bio-logically important human plasma proteins even in the presence of α-macroglobulin, the sole plasma inhibitor of native VVP. The activities of both classical and alternative pathways of the complement cas-cade system were drastically abolished by incubation with either VVP. Furthermore, these proteases rapidly digested the Aα-chain of human fibrinogen into fragment(s) with no clotting ability. Therefore both VVPs are thought to function as a fibrinogenolytic enzyme, causing delay of the coagulation reaction. VVP and PEG1-VVP were also shown to destroy plasma proteinase inhibitors including α1-proteinase inhibitor, a major inhibitor in human plasma. Because endogenous proteolytic enzymes and their inhibitors are indis-pensable in maintaining physiological homeostasis, these findings suggest that VVP (and PEG1-VVP) may cause an imbalance of human plasma proteinase-proteinase inhibitor systems, thus eliciting an immunocompromised state in the host and facilitating the development of a systemic V. vulnificus infection such as septicemia.
|Number of pages||8|
|Journal||MICROBIOLOGY and IMMUNOLOGY|
|Publication status||Published - Jan 1 1995|
- Proteinase inhibitor
- Vibrio vulnificus
ASJC Scopus subject areas