Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0849640 (skin damage)
 1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vibrio vulnificus wound infection is characterized by an intense acute cellulitis which spreads along the subcutaneous tissue with severe tissue destruction. Toxins produced by the bacteria appear to be involved in the pathogenesis of skin necrosis and to facilitate microbial dissemination in vivo. We report microscopic studies of mouse skin damage caused by a single intradermal injection of V. vulnificus or of an extracellular metalloprotease isolated from this organism. The gene encoding 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 injection of this preparation resulted in marked edematous changes of the skin, which extended throughout the dermis and subcutaneous tissues and into adjacent muscles. The collagen and elastic fibers degenerated and some muscle cells even appeared necrotic. Blood vessels became congested, with moderate perivascular neutrophil and mononuclear cell infiltration. There was no evidence of necrotic changes in the blood vessel itself. These results show that the damage to the connective tissues caused by V. vulnificus is at least partly attributable to its protease. Therefore, the protease seems to be an important virulence factor of this microbe.
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PMID:Mouse skin damage caused by a recombinant extracellular metalloprotease from Vibrio vulnificus and by V. vulnificus infection. 930 19

Bacteria of the genus Vibrio are normal habitants of the aquatic environment and play roles for biocontrole of aquatic ecosystem, but some species are believed to be human pathogens. These species can be classified into two groups according to the types of diseases they cause: the gastrointestinal infections and the extraintestinal infections. The pathogenic species produce various pathogenic factors including enterotoxin, hemolysin, cytotoxin, protease, siderophore, adhesive factor, and hemagglutinin. We studied various pathogenic factors of vibrios with special emphasis on protease and hemolysin of V. vulnificus. V. vulnificus is now recognized as being among the most rapidly fatal of human pathogens, although the infection is appeared in patients having underlying disease(s) such as liver dysfunction, alcoholic cirrhosis or haemochromatosis. V. vulnificus protease (VVP) is thought to be a major toxic factor causing skin damage in the patients having septicemia. VVP is a metalloprotease and degrades a number of biologically important proteins including elastin, fibrinogen, and plasma proteinase inhibitors of complement components. VVP causes skin damages through activation of the Factor XII-plasma kallikrein-kinin cascade and/or exocytotic histamine release from mast cells, and a haemorrhagic lesion through digestion of the vascular basement membrane. Thus, the protease is the most probable candidate for tissue damage and bacterial invasion during an infection. Pathogenic roles and functional mechanism of other factors including hemolysins of V. vulnificus and V. mimicus are also shown in this review article.
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PMID:[Pathogenic factors of vibrios with special emphasis on Vibrio vulnificus]. 1599 10

Bacteria in the genus Vibrio produce extracellular proteolytic enzymes to obtain nutrients via digestion of various protein substrates. However, the enzymes secreted by human pathogenic species have been documented to modulate the bacterial virulence. Several species including Vibrio cholerae and V. vulnificus are known to produce thermolysin-like metalloproteases termed vibriolysin. The vibriolysin from V. vulnificus, a causative agent of serious systemic infection, is a major toxic factor eliciting the secondary skin damage characterized by formation of the hemorrhagic brae. The vibriolysin from intestinal pathogens may play indirect roles in pathogenicity because it can activate protein toxins and hemagglutinin by the limited proteolysis and can affect the bacterial attachment to or detachment from the intestinal surface by degradation of the mucus layer. Two species causing wound infections, V. alginolyticus and V. parahaemolyticus, produce another metalloproteases so-called collagenases. Although the detailed pathological roles have not been studied, the collagenase is potent to accelerate the bacterial dissemination through digestion of the protein components of the extracellular matrix. Some species produce cymotrypsin-like serine proteases, which may also affect the bacterial virulence potential. The intestinal pathogens produce sufficient amounts of the metalloprotease at the small intestinal temperature; however, the metalloprotease production by extra-intestinal pathogens is much higher around the body surface temperature. On the other hand, the serine protease is expressed only in the absence of the metalloprotease.
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PMID:Extracellular proteolytic enzymes produced by human pathogenic vibrio species. 2430 21

Vibrio vulnificus, a gram-negative halophilic estuarine bacterium, is an opportunistic human pathogen that causes rapidly progressive fatal septicemia and necrotizing wound infection. This species also causes hemorrhagic septicemia called vibriosis in cultured eels. It has been proposed that a range of virulence factors play roles in pathogenesis during human and/or eel infection. Among these factors, a metalloprotease (V. vulnificus protease [VVP]) and a cytolytic toxin (V. vulnificus hemolysin [VVH]) are of significant importance. VVP elicits the characteristic edematous and hemorrhagic skin damage, whereas VVH exhibits powerful hemolytic and cytolytic activities and contributes to bacterial invasion from the intestine to the blood stream. In addition, a few V. vulnificus strains isolated from diseased eels have recently been found to produce a serine protease designated as V. vulnificus serine protease (VvsA) instead of VVP. Similarly to VVP, VvsA may possess various toxic activities such as collagenolytic, cytotoxic and edema-forming activity. In this review, regulation of V. vulnificus VVP, VVH and VvsA is clarified in terms of expression at the mRNA and protein levels. The explanation is given on the basis of the quorum sensing system, which is dependent on bacterial cell density. In addition, the roles of environmental factors and global regulators, such as histone-like nucleoid structuring protein, cyclic adeno monophosphate receptor protein, RpoS, HlyU, Fur, ToxRS, AphB and LeuO, in this regulation are outlined. The cumulative impact of these regulatory systems on the pathogenicity of V. vulnificus is here delineated.
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PMID:Regulation systems of protease and hemolysin production in Vibrio vulnificus. 2811 26

Vibrio vulnificus is a human pathogen causing fatal septicemia with edematous and hemorrhagic skin damage. Among multiple virulence factors, an extracellular metalloprotease termed as V. vulnificus protease (VVP) is known to play a crucial role in eliciting the skin damage. The mature VVP (413 aa) is composed of two domains, the N-terminal core domain with proteolytic activity and the C-terminal domain mediates efficient attachment to protein substrates. However, VVP is produced as an inactive precursor (609 aa) with a signal peptide (24 aa) and propeptide (172 aa). In order to clarify the function of propeptide, a series of DNA fragments encoding the VVP precursor and its various domains were designed and the proteins were expressed in vitro by using cell-free translational system. The results indicated that the propeptide might function as an intramolecular chaperon to promote the proper folding of both N-terminal and C-terminal domains. The obtained results also suggest that the propeptide, itself was unstable and thus digested easily by the enzymes present in cell lysate used for cell-free system. Additionally, the C-terminal domain in VVP found to inhibit the folding of the N-terminal domain in absence of propeptide.
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PMID:Functional analysis of N-terminal propeptide in the precursor of Vibrio vulnificus metalloprotease by using cell-free translational system. 2963 38