[New insight from basic research of Clostridium perfringens alpha-toxin].
Clostridium perfringens causes gas gangrene with inflammatory myopathies and infrequently septicemia associated with massive intravascular hemolysis. The microorganism is known to produce a variety of toxins and enzymes that are responsible for severe myonecrotic lesions. Notably, alpha-toxin, which possesses hemolytic, necrotic and lethal activities, and phospholipase C and sphingomyelinase activities, is an important agent for the diseases. The cytokine storm induced by alpha-toxin, mainly the release of TNF-alpha, plays an important role in the death and massive hemolysis. The toxin-induced release of TNF-alpha from neutrophils and macrophages is dependent on the activation of ERK1/2 signal transduction via TrkA receptor. In addition, 14- and 15-membered macrolides specifically block the toxin-induced events through the activation of neutrophils and macrophages.
Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University.
Masataka
M
Oda
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001427:Bacterial Toxins / Q000009:adverse effects / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000009:adverse effects / Q000494:pharmacology; D003016:Clostridium perfringens / Q000472:pathogenicity*; D005738:Gas Gangrene / Q000188:drug therapy / Q000382:microbiology*; D006461:Hemolysis; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D018942:Macrolides / Q000494:pharmacology / Q000627:therapeutic use; D008264:Macrophages / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020917:Receptor, trkA / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D010738:Type C Phospholipases / Q000009:adverse effects / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D002135:Calcium-Binding Proteins; D018942:Macrolides; D014409:Tumor Necrosis Factor-alpha; D020917:Receptor, trkA; D010738:Type C Phospholipases; C040649:alpha toxin, Clostridium perfringens