Study on pathogenic role of hemolysins produced by Vibrio spp.

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We found that hemolysins produced by Vibrio spp.can be classified into two major groups : (1) Thermostable direct hemolysin (TDH) of Vibrio parahaemolyticus and its related hemolysin (TRH) and (2) El tor hemolysin of V.cholerae Ol. We studied on these two representative hemolysins and obtained following results.1.TDH and TRH(1) We discovered a new hemolysin in culture supernatant of V.parahaemolyticus and named TRH,and we also found that TRH-gene possessig bacteria always expressed urease.(2) It was demonstrated that TDH and TRH were simultaneously produced in certain strains of V.parahaemolyticus.TDH/TRH recognized a receptor which is present on membrane of not only sensitive but also resistant cell and then caused a phosphorylation of a 25kDa membrane protein through activation of protein kinase C,resulted in pore-formation which has 1-2nm inner diameter.An isogenic mutant which lost TRH gene was developed and the result of the challenge with the mutant revealed that the isogenic mutant partially lose its enteropathogenicity, suggesting the possibility that TRH actually play a role in pathogenesis of V.parahaemolyticus and that factor (s) other than TRH may also involved in the pathogenicity.2. El Tor hemolysin(1) El Tor hemolysin is produced as a Pre-protoxin (80kDa) and passed through inner membrane with a signal peptide. In periplasmic space, the molecule becomes protoxin (79kDa) after cleavage the signal peptide. The Pro-region of the hemoysin acts as a chaperon and facilitates excretion of the protoxin through ontermembrane. The protoxin was finally modified to be an active form, mature hemolysin, by releasing Pro-region from protoxin-form. This event occurred by hemagglutinin/protease produced by Vibrio cholerae.