Role of theta toxin, a sulfhydryl-activated cytolysin, in the pathogenesis of clostridial gas gangrene.
Clostridial infections cause a wide variety of dramatic infections and intoxications. In each case the major virulence factors are extracellular toxins. Clostridium perfringens produces potent exotoxins, which are its major virulence factors. theta Toxin, a thiol-activated cytolysin, causes the clear zone of hemolysis around colonies on blood-agar plates, suppresses myocardial contractility ex vivo, and induces shock within 1 to 2 hours in vivo. Low concentrations of theta toxin induce priming and degranulation of polymorphonuclear leukocytes (PMNs) and functional up-regulation of PMN-dependent adherence molecules such as the integrin CD11/CD18, whereas higher concentrations are cytotoxic. Similarly, theta toxin causes concentration- and time-dependent induction of endothelial cell synthesis of platelet-activating factor, a potent proinflammatory lipid autocoid that mediates endothelial cell-dependent adherence of PMNs. These data suggest that theta toxin in high concentrations is a potent cytolysin and promotes direct vascular injury at the site of infection. At lower concentrations theta toxin activates PMNs and endothelial cells, and in so doing promotes vascular injury distally by activating adherence mechanisms. The rapid tissue necrosis associated with C. perfringens infection may be related to progressive vascular compromise orchestrated by dysregulated host-cell responses induced by theta toxin.
Stevens
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Infectious Disease Section, Veterans Affairs Medical Center, Boise, Idaho 83702-4598.
Bryant
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D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D002448:Cell Adhesion; D003013:Clostridium / Q000472:pathogenicity; D003016:Clostridium perfringens / Q000472:pathogenicity; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D005738:Gas Gangrene / Q000209:etiology*; D006460:Hemolysin Proteins; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D012769:Shock / Q000209:etiology; D013045:Species Specificity
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C020452:Clostridium perfringens theta-toxin