Regulation systems of protease and hemolysin production in Vibrio vulnificus

Vibrio vulnificus is a gram-negative halophilic estuarine bacterium. It is an opportunistic human pathogen causing rapidly progressive fatal septicemia and necrotizing wound infection. This species also causes hemorrhagic septicemia called vibriosis in cultured eels. A range of virulence factors have been proposed to play a role in pathogenesis of the bacterium during human and/or eel infection. Among these factors, the metalloprotease (V. vulnificus protease: VVP) and the cytolytic toxin (V. vulnificus hemolysin: VVH) are significantly important. VVP elicits the characteristic edematous and hemorrhagic skin damage. On the other hand, VVH exhibits powerful hemolytic and cytolytic activities and it also contributes to the bacterial invasion from the intestine to the blood stream. In addition, a few V. vulnificus strains isolated from diseased eels were recently found to produce a serine protease termed as V. vulnificus serine protease (VvsA) instead of VVP. Similar to VVP, VvsA may also possess various toxic activities such as collagenolytic, cytotoxic and edema-forming activity. In this review, we clarify the regulation of V. vulnificus VVP, VVH and VvsA in terms of expression at mRNA and protein level. The explanation is given on the basis of quorum sensing system, which is dependent on the bacterial cell density. In addition, we also outline the role of environmental factors and global regulators, such as histone-like nucleoid structuring protein, cyclic AMP receptor protein, RpoS, HlyU, Fur, ToxRS, AphB and LeuO, in this regulation. Altogether, we compiled the cumulative impact of these regulatory systems on the pathogenicity of V. vulnificus.