Vibrio vulnificus may produce a metalloprotease causing an edematous skin lesion in vivo

Miyoshi, Shin Ichi

doi:10.1016/0378-1097(94)90311-5

Cited by 13 publications

(15 citation statements)

References 7 publications

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“…Several studies have demonstrated numerous activities of metalloproteases of V. vulnificus when they are injected into animals (17,23,(25)(26)(27)(28)32). The effects observed were consistent with the pathogenesis of infection in animals, including vaso- , and KC64(pRKY980) (C) were analyzed.…”

Section: Resultsmentioning

confidence: 99%

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Construction and Phenotypic Evaluation of aVibrio vulnificus vvpEMutant for Elastolytic Protease

et al. 2000

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Vibrio vulnificus is an opportunistic gram-negative pathogen that commonly contaminates oysters. Predisposed individuals who consume raw oysters can die within days from sepsis, and even otherwise healthy people are susceptible to serious wound infection after contact with contaminated seafood or seawater. Numerous secreted and cell-associated virulence factors have been proposed to account for the fulminating and destructive nature of V. vulnificus infections. Among the putative virulence factors is an elastolytic metalloprotease. We cloned and sequenced the vvpE gene encoding an elastase of V. vulnificus ATCC 29307. The functions of the elastase were assessed by constructing vvpE insertional knockout mutants and evaluating phenotypic changes in vitro and in mice. Although other types of protease activity were still observed in vvpE mutants, elastase activity was completely absent in the mutants and was restored by reintroducing the recombinant vvpE gene. In contrast to previous characterization of elastase as a potential virulence factor, which was demonstrated by injecting the purified protein into animals, inactivation of the V. vulnificus vvpE gene did not affect the ability of the bacteria to infect mice and cause damage, either locally in subcutaneous tissues or systemically in the liver, in both iron-treated and normal mice. Furthermore, a vvpE mutant was not affected with regard to cytolytic activity toward INT407 epithelial cells or detachment of INT407 cells from culture dishes in vitro. Therefore, it appears that elastase is less important in the pathogenesis of V. vulnificus than would have been predicted by examining the effects of administering purified proteins to animals. However, V. vulnificus utilizes a variety of virulence factors; hence, the effects of inactivation of elastase alone could be masked by other compensatory virulence factors.The pathogenic marine bacterium Vibrio vulnificus is the causative agent of food-borne diseases such as life-threatening septicemia and possibly gastroenteritis in individuals with underlying predisposing conditions such as liver damage, excess levels of iron, and immunocompromised conditions (2, 14). Wound infections result from exposure to seawater or from the handling of shellfish contaminated with V. vulnificus. Mortality from septicemia is very high (Ͼ50%), and death may occur within 1 to 2 days after the first signs of illness (14,47). Several potential virulence factors including an endotoxin, a polysaccharide capsule (46,55,57), iron-sequestering systems (19, 54), a cytolytic hemolysin (43, 53), an elastase (16, 24, 36), a phospholipase A 2 (48), and other exotoxins have been identified for V. vulnificus. However, to date, only the capsule (55) and ironsequestering systems (19) have been confirmed as virulence factors by using the molecular version of Koch's postulates (6, 11), in which mutations are constructed in genes encoding putative virulence factors, followed by complementation of any observed attenuating phenotypes. It is interesting that a m...

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Section: Resultsmentioning

confidence: 99%

“…The V. vulnificus elastase activity is from a neutral metalloprotease, and the characteristics of the protease as a potential virulence factor have been studied primarily using the purified protein in animal models (17,23,(25)(26)(27)(28)32…”

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confidence: 99%

Construction and Phenotypic Evaluation of aVibrio vulnificus vvpEMutant for Elastolytic Protease

et al. 2000

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“…As well as V. vulnificus metalloprotease (Miyoshi and Shinoda, 1992;Miyoshi et al, 1994), V. parahaemolyticus serine protease could not generate significant amounts of plasma kallikrein because of quickly inactivation by α M (data not shown). However, as shown in Fig.…”

Section: Activation and Fragmentation Of Human Zymogens By V Parahaementioning

confidence: 96%

Generation of active fragments from human zymogens in the brady kinin-generating cascade by extracellular proteases from Vibrio vulnificus and V. parahaemolyticus

Miyoshi

Watanabe

Kawase

et al. 2004

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Vibrio vulnificus is an opportunistic human pathogen causing septicemia, and the infection is characterized by formation of the edematous skin lesions on limbs. This pathogenic species secretes a thermolysin-like metalloprotease as a virulence determinant. The metalloprotease was confirmed to activate human factor XII-plasma kallikrein-kinin cascade that results in liberation of bradykinin, a chemical mediator enhancing the vascular permeability, from high-molecular weight kininogen. Namely, the metalloprotease showed to generate active fragments by cleavage of Arg-Ile, Arg-Val or Gly-Leu peptide bond in human zymogens (plasma prekallikrein and factor XII). In spite of induction of the sufficient vascular permeability-enhancing and edema-forming reaction in the guinea pig model, a serine protease from V. parahaemolyticus, a human pathogen causing primarily watery diarrhea, showed far less ability to activate and to cleave the human zymogens. These results in part may explain why only V. vulnificus often causes serious edematous skin damages in humans.

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“…V. vulnificus infection is characterized by a high fatality rate of 70% and the primary attack against people who are immunocom-promised or have underlying diseases such as liver cirrhosis or hemochromatosis (Hollis et al, 1976;Blake et al, 1979;Park et al, 1991;Oliver et al, 1995). A variety of factors, including an extracellular cytolysin (Gray and Kreger, 1985), an elastolytic protease (Miyoshi et al, 1992), and resistance to phagocytosis (Yoshida et al, 1985) have all been implicated as possible virulence determinants for V. vulnificus septicemia in animal models. Kreger and Lockwood (1981) demonstrated that V. vulnificus cytolysin (VVC) showed hemolytic and lethal activity, and acted as vascular permeability factor.…”

Section: Introductionmentioning

confidence: 99%

Cholesterol induce oligomerization of Vibrio vulnificus cytolysin specifically

Kim

Kim²

2002

Exp Mol Med

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Vibrio vulnificus cytolysin (VVC) has been implicated as one of the important virulence determinants of V. vulnificus that causes serious septicemia and wound infection. An attempt was made to investigate that VVC could act as a ligand which stimulates intracellular signaling systems. Cholesterol dose-dependently blocked VVC hemolytic activity through oligomerization of cytolysin. Among cholesterol derivatives including 7-dehydrocholesterol, cholesteryl esters, deoxycholate, and cholestane tested, only 7-dehydrocholesterol induced oligomerization as well as inactivation of VVC. These results show that oligomerization of VVC is completely dependent on three-dimensional structure of cholesterol where specific interaction of cholesterol at oligomerization sites of VVC is very selective. These findings support the idea that cholesterol which constitute many of cellular plasma membrane could be a receptor of VVC on plasma membrane of target cells.

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Vibrio vulnificus may produce a metalloprotease causing an edematous skin lesion in vivo

Cited by 13 publications

References 7 publications

Construction and Phenotypic Evaluation of aVibrio vulnificus vvpEMutant for Elastolytic Protease

Construction and Phenotypic Evaluation of aVibrio vulnificus vvpEMutant for Elastolytic Protease

Generation of active fragments from human zymogens in the brady kinin-generating cascade by extracellular proteases from Vibrio vulnificus and V. parahaemolyticus

Cholesterol induce oligomerization of Vibrio vulnificus cytolysin specifically

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