Studies on the Processes of Construction of Active Structure of Bacterial Enterotoxin and of the Secretion to Milieu

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Several gram-negative bacteria cause severe diarrhea in human. Many of these enteric bacteria produce enterotoxins into outside of the cells, which are mainly responsible for the diarrhea induced by these bacteria. These enterotoxins are protein. In gram-negative bacteria, it is rare that the protein synthesized in cytoplasm emerges into the outside of cells. In order to emerge in the outside of the cell, the toxin must cross two membranes, inner membrane and outer membrane. And the toxins must be folded into the proper structure during the secretion. The process is called "maturation pathway of toxin". If the toxin failed to become mature toxin, the bacteria would lose the pathogenicity. Therefore, the maturation pathway of the toxin is closely related with the virulence of the bacteria.We examined the maturation pathway of two toxins. One is heat-stable enterotoxin of Escherichia coli (ST) and the other is enterotoxin of Aeromonas sobria. From the study on the former toxin, we found that ST was produced as precursor and processed in periplasm. Then, the intramolecular disulfide bonds are formed in the space by the action of DsbA and the STs cross the outer membrane though the tunnel of TolCs embedded in outer membrane.The study on the enterotoxin of Aeromonas sobria showed that the toxin form dimer in periplasm. The mutation analysis revealed that the carboxy terminal region of the toxin plays an important role in the dimerization. As the monomers of the enterotoxinis are easily digested in cells by proteases and never appear in culture medium, the carboxy terminal region of the hemolysin is important region for the secretion of hemolysin into culture medium.