Recent development for involvement of alpha-toxin in infectious diseases caused by Clostridium perfringens

Jun Sakurai

Department of Microbiology, Faculty of pharmaceutical Sciences,

Tokushima Bunri University

Clostridium perfringens alpha-toxin is an important agent of gas gangrene with inflammatory myopathies and massive hemolysis. We have reported that the toxin induces various actions by stimulating production of DG via G-protein and phosphorylating PDK1 via TrkA. Cytokines are immunoregulatory factors with a potent inflammatory action, mediating the immune/metabolic response and fueling septic shock, multiple organ dysfunction syndromes, and/or multiple organ failure. Macrolides as erythromycin (ERM) are known to be effective against diffuse panbronchiolitis characterized by chronic inflammation with inflammatory-cell infiltration. We show that that ERM inhibits the toxin-induced O^2- production in neutrophils and release of proinflammatory cytokines (TNFα、IL-1β) from neutrophils and that the injection of ERM into mice results in strong inhibitory effect on the alpha-toxin-induced hemolysis and death. The observation suggests that the administration of ERM is an effective treatment for infectious diseases caused by the microorganism.